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1
Xiao, Xiao, James Trevor Oswald, Ting Wang, Weina Zhang, and Wenliang Li. "Use of Anticancer Platinum Compounds in Combination Therapies and Challenges in Drug Delivery." Current Medicinal Chemistry 27, no. 18 (June 3, 2020): 3055–78. http://dx.doi.org/10.2174/0929867325666181105115849.
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As one of the leading and most important metal-based drugs, platinum-based pharmaceuticals are widely used in the treatment of solid malignancies. Despite significant side effects and acquired drug resistance have limited their clinical applications, platinum has shown strong inhibitory effects for a wide assortment of tumors. Drug delivery systems using emerging technologies such as liposomes, dendrimers, polymers, nanotubes and other nanocompositions, all show promise for the safe delivery of platinum-based compounds. Due to the specificity of nano-formulations; unwanted side-effects and drug resistance can be largely averted. In addition, combinational therapy has been shown to be an effective way to improve the efficacy of platinum based anti-tumor drugs. This review first introduces drug delivery systems used for platinum and combinational therapeutic delivery. Then we highlight some of the recent advances in the field of drug delivery for combinational therapy; specifically progress in leveraging the cytotoxic nature of platinum-based drugs, the combinational effect of other drugs with platinum, while evaluating the drug targeting, side effect reducing and sitespecific nature of nanotechnology-based delivery platforms.
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Hassan Marouf, Bushra, and Mayyadah Mahmood Ali. "Prevention and Management of Platinum Compounds-Induced Neurotoxicity." Al-Rafidain Journal of Medical Sciences ( ISSN: 2789-3219 ) 1 (November 22, 2021): 102–9. http://dx.doi.org/10.54133/ajms.v1i.43.
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Oncologists considered platinum-based medicines as potent cytotoxic agents. Despite their efficacy in combination chemotherapy regimens for many solid tumors, they have many substantial side effects that limit their use. There is no known prophylactic strategy for platinum drugs-induced neurotoxicity, which limit a therapeutic dose benefit. This review highlights the etiology of platinum-drugs-induced neuropathy, and covers the preventative and therapeutic options for cancer patients. It focuses on clinical studies conducted between 2010 and 2020. Loss of functional indications such as touch, vibration and joint location, as well as diminished or missing deep tendon reflexes in the upper and lower limbs are all markers of neurotoxicity. These side effects may last for months or years after treatment, lower quality of life, and creating a substantial survivorship issue. DNA damage, oxidative stress, mitochondrial dysfunction, dysregulation of intracellular signaling, impairment of voltage gated ion channel function, and neuro-inflammation have all been proposed as mechanisms for chemotherapy-induced peripheral neuropathy (CIPN). There are no proven pharmaceutical or nutritional therapies to prevent CIPN. Several anti-CIPN medications have been investigated, but either had no effect or had an effect in a limited sample study. Supportive care medications such anti-epileptics and antidepressants are used to treat CIPN.
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Makovec, Tomaz. "Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy." Radiology and Oncology 53, no. 2 (March 28, 2019): 148–58. http://dx.doi.org/10.2478/raon-2019-0018.
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AbstractBackgroundPlatinum-based anticancer drugs are widely used in the chemotherapy of human neoplasms. The major obstacle for the clinical use of this class of drugs is the development of resistance and toxicity. It is therefore very important to understand the chemical properties, transport and metabolic pathways and mechanism of actions of these compounds. There is a large body of evidence that therapeutic and toxic effects of platinum drugs on cells are not only a consequence of covalent adducts formation between platinum complexes and DNA but also with RNA and many proteins. These processes determine molecular mechanisms that underlie resistance to platinum drugs as well as their toxicity. Increased expression levels of various transporters and increased repair of platinum-DNA adducts are both considered as the most significant processes in the development of drug resistance. Functional genomics has an increasing role in predicting patients’ responses to platinum drugs. Genetic polymorphisms affecting these processes may play an important role and constitute the basis for individualized approach to cancer therapy. Similar processes may also influence therapeutic potential of nonplatinum metal compounds with anticancer activity.ConclusionsCisplatin is the most frequently used platinum based chemotherapeutic agent that is clinically proven to combat different types of cancers and sarcomas.
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Jurgens, Sophie, Fritz E. Kuhn, and Angela Casini. "Cyclometalated Complexes of Platinum and Gold with Biological Properties: State-of-the-Art and Future Perspectives." Current Medicinal Chemistry 25, no. 4 (February 12, 2018): 437–61. http://dx.doi.org/10.2174/0929867324666170529125229.
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Background: The inherent problems accompanying chemotherapy necessitate the development of new anticancer approaches. The development of compounds that can disrupt cancerous cellular machinery by novel mechanisms, via interactions with proteins and non-canonical DNA structures (e.g. G-quadruplexes), as well as by alteration of the intracellular redox balance, is nowadays focus of intense research. In this context, organometallic compounds of the noble metals Pt and Au have become prominent experimental therapeutic agents. This review provides an overview of the Pt(II) and Au(III) cyclometalated compounds with a chelating ring containing a strong C-M σ -bond to improve the stability of the compounds with respect to ligand exchange reactions and biological reduction. Furthermore, these properties can be easily tuned by modification of either the anionic cyclometalated or the ancillary ligands. Special focus has been set to C^N, C^N^C, C^N^N and C^N^S platinum(II) and gold(III) pincer complexes regarding their synthesis and biological mechanisms of action as anticancer agents. Methods: A structured search of both chemical and medicinal databases for peerreviewed research literature has been conducted. The quality of retrieved papers was appraised using standard tools. The synthesis as well as the chemical and biological properties of the described compounds were carefully reviewed and described. The findings were outlined using a conceptual framework. Results: In this review we included 155 papers, the majority originating from high-impact papers on the synthesis and biological modes of platinum(II) and gold(III) compounds. Among them, 17 papers were highlighted to give an introduction to the use of Pt and Au compounds with medicinal properties, mainly focussing on coordination compounds. The synthesis and medicinal properties of organometallic compounds of various metals (such as Fe, Ru, Ti) were outlined in 51 papers. These compounds included metallocenes, metallo- arenes, metallo-carbonyls, metallo-carbenes (e.g. N-heterocyclic carbenes), and alkynyl complexes. The C^N, C^N^C, C^N^N and C^N^S pincer complexes of platinum( II) (46 papers) and gold(III) (44 papers) were discussed concerning their synthesis, stability and advantages to develop therapeutic compounds. We strove to show the consistent development of C^N, C^N^C, C^N^N and C^N^S platinum(II) and gold(III) pincer complexes regarding their synthesis and biological modes from the early beginnings to the most recent findings. Conclusion: This review supplies a profound overview of the development of organometallic compounds for medicinal purposes, setting special focus to the synthesis and stability of C^N, C^N^C, C^N^N and C^N^S pincer complexes of platinum(II) and gold(III) and their use as anticancer agents.
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Roszczenko, Piotr, Olga Klaudia Szewczyk, Robert Czarnomysy, Krzysztof Bielawski, and Anna Bielawska. "Biosynthesized Gold, Silver, Palladium, Platinum, Copper, and Other Transition Metal Nanoparticles." Pharmaceutics 14, no. 11 (October 25, 2022): 2286. http://dx.doi.org/10.3390/pharmaceutics14112286.
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Nanomedicine is a potential provider of novel therapeutic and diagnostic routes of treatment. Considering the development of multidrug resistance in pathogenic bacteria and the commonness of cancer, novel approaches are being sought for the safe and efficient synthesis of new nanoparticles, which have multifaceted applications in medicine. Unfortunately, the chemical synthesis of nanoparticles raises justified environmental concerns. A significant problem in their widespread use is also the toxicity of compounds that maintain nanoparticle stability, which significantly limits their clinical use. An opportunity for their more extensive application is the utilization of plants, fungi, and bacteria for nanoparticle biosynthesis. Extracts from natural sources can reduce metal ions in nanoparticles and stabilize them with non-toxic extract components.
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Wimberger, Pauline, Barbara Klink, Konrad Gruetzmann, Julian Puppe, Daniel Klotz, Evelin Schroeck, Jan Dominik Kuhlmann, and Sarah Schott. "The activity of the conjugated antimetabolite 5-FdU-ECyd against platinum-resistant ovarian cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e17077-e17077. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e17077.
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e17077 Background: Primary or secondary resistance to platinum-based chemotherapy is an important clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, the development of innovative drugs against platinum resistance is urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and is subsequently cleaved into several active cytostatic metabolites. Our in vitro study evaluates the effects of the conjugated antimetabolite 5-FdU-ECyd, consisting of 2-deoxy-5-fluorouridine (5-FdU) and ethynylcytidine (ECyd), on platinum-resistant OC cells. Methods: In vitro assays and RNA-Seq (Illumina) were applied for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis as well as independent platinum-resistant Skov-3-IP OC cells. Results: Nano molar 5-FdU-ECyd concentrations induced a rapid dose-dependent decline of cell viability in platinum-sensitive and platinum-resistant OC cells. The cytotoxicity of 5-FdU-ECyd was accompanied by the formation of DNA double strand breaks and by the induction of apoptosis, indicated by a strong increase of pro-apoptotic molecular markers (caspase-3/7 activation, PARP-cleavage). Moreover, 5-FdU-ECyd efficiently decreased cell migration of platinum-resistant OC cells and inhibited other tumor-associated cellular functions, such as clonogenic or spheroidal growth. Transcriptome analysis indicated that, independently of platinum-resistance status, 5-FdU-ECyd influences distinct cellular pathways, involved in cell cycle regulation, apoptosis, DNA-damage response and RNA/pyrimidine metabolism. Combination treatment of 5-FdU-ECyd and platin did not show a synergistic cellular response, suggesting the potential use of 5-FdU-ECyd as a monotherapeutic agent. Conclusions: Our data provide a rationale to characterize the effect of 5-FdU-ECyd in a pre-clinical in vivo setting. We hypothesize that this conjugate is a promising therapeutic option for OC patients with resistance to conventional platinum-based chemotherapy.
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Maiorano, Brigida Anna, Ugo De Giorgi, Davide Ciardiello, Giovanni Schinzari, Antonio Cisternino, Giampaolo Tortora, and Evaristo Maiello. "Immune-Checkpoint Inhibitors in Advanced Bladder Cancer: Seize the Day." Biomedicines 10, no. 2 (February 9, 2022): 411. http://dx.doi.org/10.3390/biomedicines10020411.
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Background: In advanced bladder cancer (BCa), platinum-based chemotherapy represents the first-choice treatment. In the last ten years, immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape of many solid tumors. Our review aims to summarize the main findings regarding the clinical use of ICIs in advanced BCa. Methods: We searched PubMed, Embase, and Cochrane databases, and conference abstracts from international congresses (ASCO, ESMO, ASCO GU) for clinical trials, focusing on ICIs as monotherapy and combinations in metastatic BCa. Results: 18 studies were identified. ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, atezolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab) were used. Survival outcomes have been improved by second-line ICIs, whereas first-line results are dismal. Avelumab maintenance in patients obtaining disease control with chemotherapy has achieved the highest survival rates. Conclusions: ICIs improve survival after platinum-based chemotherapy. Avelumab maintenance represents a new practice-changing treatment. The combinations of ICIs and other compounds, such as FGFR-inhibitors, antibody-drug conjugates, and anti-angiogenic drugs, represent promising therapeutic approaches. Biomarkers with predictive roles and sequencing strategies are warranted for best patient selection.
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Marcu, Loredana G. "Gender and Sex-Related Differences in Normal Tissue Effects Induced by Platinum Compounds." Pharmaceuticals 15, no. 2 (February 20, 2022): 255. http://dx.doi.org/10.3390/ph15020255.
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Gender medicine in the field of oncology is an under-researched area, despite the existing evidence towards gender-dependent response to therapy and treatment-induced adverse effects. Oncological treatment aims to fulfil its main goal of achieving high tumour control by also protecting normal tissue from acute or chronic damage. Chemotherapy is an important component of cancer treatment, with a large number of drugs being currently in clinical use. Cisplatin is one of the most commonly employed chemotherapeutic agents, used either as a sole drug or in combination with other agents. Cisplatin-induced toxicities are well documented, and they include nephrotoxicity, neurotoxicity, gastrointestinal toxicity, ototoxicity, just to name the most frequent ones. Some of these toxicities have short-term sequelae, while others are irreversible. Furthermore, research showed that there is a strong gender-dependent aspect of side effects caused by the administration of cisplatin. While evidence towards sex differences in animal models is substantial, clinical studies considering sex/gender as a variable factor are limited. This work summarises the current knowledge on sex/gender-related side effects induced by platinum compounds and highlights the gaps in research that require more attention to open new therapeutic possibilities and preventative measures to alleviate normal tissue toxicity and increase patients’ quality of life in both males and females.
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Faraoni, Isabella, and Grazia Graziani. "Role of BRCA Mutations in Cancer Treatment with Poly(ADP-ribose) Polymerase (PARP) Inhibitors." Cancers 10, no. 12 (December 4, 2018): 487. http://dx.doi.org/10.3390/cancers10120487.
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Inhibition of poly(ADP-ribose) polymerase (PARP) activity induces synthetic lethality in mutated BRCA1/2 cancers by selectively targeting tumor cells that fail to repair DNA double strand breaks (DSBs). Clinical studies have confirmed the validity of the synthetic lethality approach and four different PARP inhibitors (PARPi; olaparib, rucaparib, niraparib and talazoparib) have been approved as monotherapies for BRCA-mutated or platinum-sensitive recurrent ovarian cancer and/or for BRCA-mutated HER2-negative metastatic breast cancer. PARPi therapeutic efficacy is higher against tumors harboring deleterious germline or somatic BRCA mutations than in BRCA wild-type tumors. BRCA mutations or intrinsic tumor sensitivity to platinum compounds are both regarded as indicators of deficiency in DSB repair by homologous recombination as well as of favorable response to PARPi. However, not all BRCA-mutated or platinum-responsive patients obtain clinical benefit from these agents. Conversely, a certain percentage of patients with wild-type BRCA or platinum-resistant tumors can still get benefit from PARPi. Thus, additional reliable markers need to be validated in clinical trials to select patients potentially eligible for PARPi-based therapies, in the absence of deleterious BRCA mutations or platinum sensitivity. In this review, we summarize the mechanisms of action of PARPi and the clinical evidence supporting their use as anticancer drugs as well as the additional synthetic lethal partners that might confer sensitivity to PARPi in patients with wild-type BRCA tumors.
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Krasnopolsky, Yu, D. Pylypenko, and G. Grigoryeva. "NANOMEDICINE IN ANTICANCER THERAPY." Bulletin of the National Technical University "KhPI". Series: Chemistry, Chemical Technology and Ecology 1, no. 7 (December 30, 2022): 3–13. http://dx.doi.org/10.20998/2079-0821.2022.01.
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The use of liposomal nanoparticles as a drug delivery system today is a promising area of modern nanopharmacology, in particular in the development of antitumor drugs. Liposomal forms of antitumor active pharmaceutical ingredients are characterized by reduced toxicity, stability, and increased antitumor activity of nanoparticle-encapsulated antitumor agent, prolonged action of the drug. Commercially available liposomal anticancer drugs are passively targeted drugs that accumulate in cells by passive diffusion in tumor cells due to the EPR effect of the vascular system. This review presents data from the study of antitumor activity of liposomal drugs conducted by Ukrainian scientists in recent decades. Today, the antitumor activity of liposomal forms of therapeutic agents of various natures has been proven, among them are anthracycline antibiotics, platinum drugs, semisynthetic alkaloid derivatives, natural polyphenolic antioxidants, etc. Thus, the encapsulation of doxorubicin hydrochloride in liposomes has reduced its cardiotoxicity and other side effects, provided an opportunity to treat doxorubicin-resistant tumors. Liposomal forms of complex platinum compounds, in particular cisplatin, have been shown to be more effective than free forms of cytostatics in the treatment of cisplatin-resistant ovarian cancer. The use of polyphenolic antioxidants, quercetin and curcumin, in complex therapy can not only enhance the antitumor effect, but also have a protective effect on healthy tissues and organs.
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Varela-Castillo, O., P. Cordero, G. Gutiérrez-Iglesias, I. Palma, I. Rubio-Gayosso, E. Meaney, I. Ramirez-Sanchez, F. Villarreal, G. Ceballos, and N. Najera. "CHARACTERIZATION OF THE CYTOTOXIC EFFECTS OF THE COMBINATION OF CISPLATIN AND FLAVANOL (-)-EPICATECHIN ON HUMAN LUNG CANCER CELL LINE A549. AN ISOBOLOGRAPHIC APPROACH." Experimental Oncology 40, no. 1 (March 22, 2018): 19–23. http://dx.doi.org/10.31768/2312-8852.2018.40(1):19-23.
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Background: Among malignancies, lung cancer is a leading cause of death. Platinum-based therapeutic compounds used to treat lung cancer have not been able to increase the survival of patients and such compounds have a high incidence of adverse and toxic effects. It has been proposed that flavonoids such as catechins may significantly reduce the risk of developing cancer, alongside with other health benefits. The aim of this work was to determine the effect of (-)-epicatechin, the main flavanol found in cocoa, on the proliferation of the lung non-small cell adenocarcinoma cancer cell line A549, and to determine its effects when added simultaneously with cisplatin. Materials and Methods: Concentration-response curves for cisplatin and epicatechin were obtained, inhibitory concentrations calculated and an isobolographic analysis was then performed. Results: We found that epicatechin has a concentration-dependent inhibitory effect on proliferation of tumor cells and the isobolographic analysis reveals that the effect of its combination with cisplatin is synergistic. It was also observed that epicatechin promotes cell death by apoptosis. Conclusions: Epicatechin might be considered for future studies to explore its possible use as coadjuvant in cisplatin-based treatments.
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P., Pramila, Anju Abraham, Sunita Pawar, Vibha Bafna, and Monika S. Bansal. "TO STUDY THE THERAPEUTIC MANAGEMENT, DRUG RELATED PROBLEMS AND CONCOMITANT USE OF DRUGSIN PATIENTS WITH CANCER." International Journal of Pharmacy and Pharmaceutical Sciences 9, no. 6 (June 1, 2017): 139. http://dx.doi.org/10.22159/ijpps.2017v9i6.18207.
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Objective: To study the prescribing patterns of chemotherapeutic drugs, concomitant drugs and to determine the drug-related problems in cancer patients.Methods: A prospective and retrospective observational study was conducted over a period of 6 mo in a tertiary care teaching hospital, Pune after ethical approval and informed consent. Patients were then interviewed for patient information like demographics, treatment, and associated drug related problems using specially designed proforma and then required data was introduced in Microsoft excel spreadsheets.Results: Out of 60 patients 50 were enrolled in this study during which 9 different sites of cancer were examined. The maximum number of patients with cancer resides in the age group of 51-60 y (32%) and more common in females in 27 (54%). The most prevalent risk factor and co-morbidity encountered were tobacco chewing 13 (26%) and hypertension 8 (16%), respectively. On the further evaluation of data, the findings suggested that the majority of patients were prescribed with an alkylating group of anti-neoplastic agents, paclitaxel+platinum-based compound regimen, and the drug paclitaxel. On screening, 167 drug interactions were observed, of these most of the interactions were in the moderate category. The most common organ system affected was gastrointestinal system 135 (30.80%) whereas the prevalent toxicity was hyperuricemia. Polypharmacy was not observed, whereas antacid (ranitidine) was frequently prescribed during hospitalisation and discharge.Conclusion: This study has highlighted certain facts and drawbacks in medication-related care which can be addressed by conducting future studies in cancer care in order to provide patient-specific outcomes.
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González-García, J., B. Alonso-Alvarez, GJ Nazco-Casariego, N. Batista-López, and F. Guttiérrez-Nicolás. "Plasma levels of trastuzumab in gastric cancer: Case report." Journal of Oncology Pharmacy Practice 23, no. 8 (September 23, 2016): 635–37. http://dx.doi.org/10.1177/1078155216670228.
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Introduction The use of trastuzumab with a fluoropyrimidine and platinum compound is currently the standard first-line treatment of patients with metastatic HER2-positive gastric cancer, but it appears that serum levels of trastuzumab determine the clinical effectiveness of this treatment, affecting progression-free survival and overall survival. Case report We report the case of a patient with metastatic HER2-positivegastric cancer, receiving XELOX (fluoropyrimidine and oxaliplatin) plus trastuzumab at standard doses, who presented sub-therapeutic serum levels during the first two treatment cycles and rapid disease progression (progression-free survival = 5.6 months). Discussion This case reveals a possible cause of poor effectiveness of trastuzumab treatment for metastatic gastric cancer in some patients, namely low circulating levels of the drug. It highlights the importance of monitoring as a possible tool for individual dose adjustment to optimize this therapy.
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Dasari, Shaloam, Sylvianne Njiki, Ariane Mbemi, Clement G. Yedjou, and Paul B. Tchounwou. "Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy." International Journal of Molecular Sciences 23, no. 3 (January 28, 2022): 1532. http://dx.doi.org/10.3390/ijms23031532.
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Cisplatin and other platinum-based drugs, such as carboplatin, ormaplatin, and oxaliplatin, have been widely used to treat a multitude of human cancers. However, a considerable proportion of patients often relapse due to drug resistance and/or toxicity to multiple organs including the liver, kidneys, gastrointestinal tract, and the cardiovascular, hematologic, and nervous systems. In this study, we sought to provide a comprehensive review of the current state of the science highlighting the use of cisplatin in cancer therapy, with a special emphasis on its molecular mechanisms of action, and treatment modalities including the combination therapy with natural products. Hence, we searched the literature using various scientific databases., such as MEDLINE, PubMed, Google Scholar, and relevant sources, to collect and review relevant publications on cisplatin, natural products, combination therapy, uses in cancer treatment, modes of action, and therapeutic strategies. Our search results revealed that new strategic approaches for cancer treatment, including the combination therapy of cisplatin and natural products, have been evaluated with some degree of success. Scientific evidence from both in vitro and in vivo studies demonstrates that many medicinal plants contain bioactive compounds that are promising candidates for the treatment of human diseases, and therefore represent an excellent source for drug discovery. In preclinical studies, it has been demonstrated that natural products not only enhance the therapeutic activity of cisplatin but also attenuate its chemotherapy-induced toxicity. Many experimental studies have also reported that natural products exert their therapeutic action by triggering apoptosis through modulation of mitogen-activated protein kinase (MAPK) and p53 signal transduction pathways and enhancement of cisplatin chemosensitivity. Furthermore, natural products protect against cisplatin-induced organ toxicity by modulating several gene transcription factors and inducing cell death through apoptosis and/or necrosis. In addition, formulations of cisplatin with polymeric, lipid, inorganic, and carbon-based nano-drug delivery systems have been found to delay drug release, prolong half-life, and reduce systemic toxicity while other formulations, such as nanocapsules, nanogels, and hydrogels, have been reported to enhance cell penetration, target cancer cells, and inhibit tumor progression.
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Lothstein, Leonard, Judith Soberman, Deanna Parke, Jatin Gandhi, Trevor Sweatman, and Tiffany Seagroves. "Pivarubicin Is More Effective Than Doxorubicin Against Triple-Negative Breast Cancer In Vivo." Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 28, no. 5 (December 10, 2020): 451–65. http://dx.doi.org/10.3727/096504020x15898794315356.
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Triple-negative breast cancer (TNBC) is unresponsive to antiestrogen and anti-HER2 therapies, requiring the use of cytotoxic drug combinations of anthracyclines, taxanes, cyclophosphamide, and platinum compounds. Multidrug therapies achieve pathological cure rates of only 2040%, a consequence of drug resistance and cumulative dose limitations necessitated by the reversible cardiotoxic effects of drug therapy. Safer and more effective treatments for TNBC are required to achieve durable therapeutic responses. This study describes the mechanistic analyses of the novel anthracycline, pivarubicin, and its in vivo efficacy against human primary TNBC. Pivarubicin directly activates PKCd, triggers rapid mitochondrial-dependent apoptosis, and circumvents resistance conferred by overexpression of P-glycoprotein, Bcl-2, Bcl-XL, and Bcr-Abl. As a consequence, pivarubicin is more cytotoxic than doxorubicin against MDA-MB-231, and SUM159 TNBC cell lines grown in both monolayer culture and tumorspheres. Comparative in vivo efficacy of pivarubicin and doxorubicin was performed in an orthotopic NSG mouse model implanted with MDA-MB-231 human TNBC cells and treated with the maximum tolerated doses (MTDs) of pivarubicin and doxorubicin. Tumor growth was monitored by digital caliper measurements and determination of endpoint tumor weight and volume. Endpoint cardiotoxicity was assessed histologically by identifying microvacuolization in ventricular cardiomyocytes. Primary tumors treated with multiple rounds of doxorubicin at MTD failed to inhibit tumor growth compared with vehicle-treated tumors. However, administration of a single MTD of pivarubicin produced significant inhibition of tumor growth and tumor regression relative to tumor volume prior to initiation of treatment. Histological analysis of hearts excised from drug- and vehicle-treated mice revealed that pivarubicin produced no evidence of myocardial damage at a therapeutic dose. These results support the development of pivarubicin as a safer and more effective replacement for doxorubicin against TNBC as well as other malignancies for which doxorubicin therapy is indicated.
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Barr, Ronald D., Dawn Chalmers, Sonja De Pauw, William Furlong, Sheila Weitzman, and David Feeny. "Health-Related Quality of Life in Survivors of Wilms’ Tumor and Advanced Neuroblastoma: A Cross-Sectional Study." Journal of Clinical Oncology 18, no. 18 (September 18, 2000): 3280–87. http://dx.doi.org/10.1200/jco.2000.18.18.3280.
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PURPOSE: In pediatric oncology, Wilms’ tumor and advanced neuroblastoma represent opposite ends of the spectra of survival probability and therapeutic intensity. Consequently, it was envisaged that survivors of Wilms’ tumor would enjoy better health status and health-related quality of life (HRQL) than survivors of advanced neuroblastoma. PATIENTS AND METHODS: Health status questionnaires were sent to the parents of all eligible children and to the children themselves if they were ≥ 8 years of age. Responses were received from 84% of 93 eligible families. Responses were converted by established algorithms into levels of two multiattribute health status classification systems known as Health Utilities Index Mark 2 and Mark 3. These systems are linked to measures of preference, in the form of multiattribute utility functions, which provide scores of morbidity for single-attribute levels and of global HRQL for comprehensive health states. RESULTS: A greater burden of morbidity was identified in the survivors of advanced neuroblastoma than in survivors of Wilms’ tumor based on the assessments of the parents of these children. In particular, survivors of advanced neuroblastoma exhibited deficits in hearing and speech. It is possible that this morbidity burden reflects the prevalent use of platinum compounds (causing ototoxicity) in this group. Within parent-child dyads there was a high level of percentage agreement on responses in all attributes except cognition. CONCLUSION: Extension of this study to a larger sample size of patients will provide clarification of these observations.
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Prasad, Sahdeo, Dan DuBourdieu, Ajay Srivastava, Prafulla Kumar, and Rajiv Lall. "Metal–Curcumin Complexes in Therapeutics: An Approach to Enhance Pharmacological Effects of Curcumin." International Journal of Molecular Sciences 22, no. 13 (June 30, 2021): 7094. http://dx.doi.org/10.3390/ijms22137094.
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Curcumin, an active component of the rhizome turmeric, has gained much attention as a plant-based compound with pleiotropic pharmacological properties. It possesses anti-inflammatory, antioxidant, hypoglycemic, antimicrobial, neuroprotective, and immunomodulatory activities. However, the health-promoting utility of curcumin is constrained due to its hydrophobic nature, water insolubility, poor bioavailability, rapid metabolism, and systemic elimination. Therefore, an innovative stride was taken, and complexes of metals with curcumin have been synthesized. Curcumin usually reacts with metals through the β-diketone moiety to generate metal–curcumin complexes. It is well established that curcumin strongly chelates several metal ions, including boron, cobalt, copper, gallium, gadolinium, gold, lanthanum, manganese, nickel, iron, palladium, platinum, ruthenium, silver, vanadium, and zinc. In this review, the pharmacological, chemopreventive, and therapeutic activities of metal–curcumin complexes are discussed. Metal–curcumin complexes increase the solubility, cellular uptake, and bioavailability and improve the antioxidant, anti-inflammatory, antimicrobial, and antiviral effects of curcumin. Metal–curcumin complexes have also demonstrated efficacy against various chronic diseases, including cancer, arthritis, osteoporosis, and neurological disorders such as Alzheimer’s disease. These biological activities of metal–curcumin complexes were associated with the modulation of inflammatory mediators, transcription factors, protein kinases, antiapoptotic proteins, lipid peroxidation, and antioxidant enzymes. In addition, metal–curcumin complexes have shown usefulness in biological imaging and radioimaging. The future use of metal–curcumin complexes may represent a new approach in the prevention and treatment of chronic diseases.
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Bossi, P., D. Parolini, C. Bergamini, L. D. Locati, E. Orlandi, M. Franceschini, M. Palazzi, P. Olmi, P. Potepan, and L. Licitra. "TPF induction chemotherapy (CT) followed by concomitant cisplatin/radiotherapy (cCTRT) in locally advanced nasopharyngeal cancer (LANPC)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 6046. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.6046.
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6046 Background: Recent meta-analysis showed better event free survival in LANPC with induction CT. In head and neck cancer, docetaxel, cisplatin and 5 FU (TPF) induction chemotherapy led to survival gain over cisplatin and 5FU alone. We studied feasibility and activity of TPF induction CT followed by cCTRT in LANPC. Methods: From October 2004 to May 2008, 45 pts with LANPC were treated at our Institution with 2 to 4 cycles (median 3) of induction TPF (docetaxel 75 mg/sm and cisplatin 75 mg/sm on day 1, and 5-FU 750 mg/sm/day ci for 96 hrs. Prophylactic ciprofloxacin was administered for 10 days each cycle, while use of G-CSF was not allowed. Following CT, pts received full doses radiotherapy (RT) concurrent with cisplatin 100 mg/sm q 21 days. Intensity modulated radiotherapy (IMRT) was delivered to 34 pts (76%). All but two pts had non-keratinizing carcinoma. Stage IV pts were 60%, stage III 34%, and 6% stage II. T4 was present in 24% and N3 disease was diagnosed in 42% of the pts. Results: TPF was well tolerated, with main toxicity consisting in neutropenia (31% G3–4). Response rate was 87%. RT dose ranged from 64 Gy to 70 Gy (median 70 Gy). Main toxicities during cCTRT were: neutropenia (38% G3, 4% G4), febrile neutropenia (11% G3), thrombocytopenia (7% G3–4) and mucositis (40% G3, 4% G4). Nasogastric tube was placed in 33% of pts and maintained for a median of 40 days. During cCTRT, platinum compounds mean dose delivery was 75%, with 6 pts shifting to carboplatin for renal function impairment. Observed late toxicities were xerostomia (G3 in 38% of cases) and peripheral neurotoxicity (G1 in 27%, G2 in 7% and G3 in 2% of the pts). After treatment completion, complete and partial response were recorded in 78% and 20% of the pts respectively, while 1 pt showed stable disease. With a median follow up of 22 months (range 7 to 47), 9 pts showed recurrence or progressive disease (7 at local and/or regional level, 2 distant metastases and 1 at both sites), with a 2-years event free survival of 78% and an overall survival of 85%. Conclusions: TPF followed by cCTRT is feasible in LANPC. In this high-stage nonendemic population local-regional disease control still remains the main therapeutic goal. Supported in part by AIRC. [Table: see text]
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Bryde, Susanne, and Anton IPM de Kroon. "Nanocapsules of platinum anticancer drugs: development towards therapeutic use." Future Medicinal Chemistry 1, no. 8 (November 2009): 1467–80. http://dx.doi.org/10.4155/fmc.09.112.
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Soejima, Takashi, and Kei-ji Iwatsuki. "Innovative Use of Palladium Compounds To Selectively Detect Live Enterobacteriaceae in Milk by PCR." Applied and Environmental Microbiology 82, no. 23 (September 23, 2016): 6930–41. http://dx.doi.org/10.1128/aem.01613-16.
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ABSTRACTEthidium monoazide and propidium monoazide (EMA and PMA) have been used in combination with PCR for more than a decade to facilitate the discrimination of live and dead bacteria (LD discrimination). These methods, however, require many laborious procedures, including the use of a darkroom. Here, we demonstrate an innovative use of palladium compounds involving lower limits of detection and quantification of targeted live cells, fewer laborious procedures, lower costs, and potentially higher-throughput analysis than the use of EMA and PMA. We have also recently reported platinum compounds for LD discrimination, but platinum compounds carry costs that are 3 times higher because of the requirement for much larger amounts for LD discrimination than palladium compounds. Palladium compounds can penetrate dead (compromised) but not live bacteria and can be chelated primarily by chromosomal DNA and cell wall transmembrane proteins, with small amounts of DNA-binding proteinsin vivo. The new mechanism for palladium compounds is obviously different from that of platinum compounds, which primarily target DNA. Combining palladium compounds with PCR (Pd-PCR) in water resulted in discrimination between live and deadEnterobacteriaceaebacteria that was much clearer than that seen with the PMA method. Pd-PCR correlated with reference plating or with the currently used PMA-PCR method for pasteurized milk, based on EN ISO 16140:2003 validation. Pd-PCR enabled us to specifically detect and assay viableEnterobacteriaceaecells at concentrations of 5 to 10 CFU/ml in milk while following U.S./EU regulations after a 4.5-h process in a typical laboratory exposed to natural or electric light, as specified by U.S./EU regulations.IMPORTANCEEthidium monoazide and propidium monoazide (EMA and PMA) facilitate the discrimination of live and dead bacteria (LD discrimination). These methods, however, require many laborious procedures, including the use of a darkroom. Here, we demonstrate an innovative use of palladium compounds involving fewer laborious procedures, lower costs, and potentially higher-throughput analysis than the use of EMA and PMA. We have also recently reported platinum compounds for LD discrimination, but platinum compounds carry costs that are 3 times higher because of the requirement for much larger amounts for LD discrimination than palladium compounds, which have also a novel reaction mechanism different from that of platinum compounds. In view of testing cost, palladium compounds are also very useful here compared with platinum compounds. Ultimately, the innovative Pd-PCR method may be also substituted for the currently used reference plating methods.
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Woźniak, Katarzyna, and Zofia Walter. "Induction of DNA-Protein Cross-Links by Platinum Compounds." Zeitschrift für Naturforschung C 55, no. 9-10 (October 1, 2000): 731–36. http://dx.doi.org/10.1515/znc-2000-9-1010.
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Abstract The differences between cis- and trans-diamminedichloroplatinum II (DDP) in forming DNA-protein cross-links in isolated human lymphocytes were investigated. Both cis- and trans-DDP can induce DNA-protein cross-links. We show that cis-DDP forms complexes between DNA and proteins faster than trans-DDP. This results from an increase in the quantity of DNA and platinum together with an increase in drug concentration. Under the same conditions trans-DDP causes a decrease in DNA-forming complexes with proteins. After a 12 h incubation of lymphocytes we observe a similar level of DNA in DNA-protein crosslinks induced by DDP isomers, but more platinum appears in complexes induced by trans- DDP. The results obtained demonstrate that the antitumor drug - cis-DDP and the clinically ineffective trans-DDP induce links between DNA and proteins in a different manner. We suggest that the therapeutic activity of ds-DDP can in part arise from rapidly forming DNA-protein complexes which can destroy the most important cellular processes, such as replication and transcription.
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Rébé, Cédric, Lucie Demontoux, Thomas Pilot, and François Ghiringhelli. "Platinum Derivatives Effects on Anticancer Immune Response." Biomolecules 10, no. 1 (December 20, 2019): 13. http://dx.doi.org/10.3390/biom10010013.
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Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells’ fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints’ expression.
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Reedijk, Jan. "Increased understanding of platinum anticancer chemistry." Pure and Applied Chemistry 83, no. 9 (March 31, 2011): 1709–19. http://dx.doi.org/10.1351/pac-con-10-11-03.
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The development of a few worldwide routinely used Pt(II) coordination compounds is described from a mechanistic point of view and related to the molecular aspects of Pt-DNA binding. Mechanistic knowledge developed from these studies is applied nowadays for the design and synthesis of new bifunctional and trifunctional compounds, aimed for use as improved anticancer drugs.
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Farrell, Nicholas P. "Preclinical perspectives on the use of platinum compounds in cancer chemotherapy." Seminars in Oncology 31 (December 2004): 1–9. http://dx.doi.org/10.1053/j.seminoncol.2004.11.004.
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Maillard, Maud, Félicien Le Louedec, Fabienne Thomas, and Etienne Chatelut. "Diversity of dose-individualization and therapeutic drug monitoring practices of platinum compounds: a review." Expert Opinion on Drug Metabolism & Toxicology 16, no. 10 (October 2, 2020): 907–25. http://dx.doi.org/10.1080/17425255.2020.1789590.
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Domínguez-Jurado, Elena, Francisco J. Cimas, José Antonio Castro-Osma, Alberto Juan, Agustín Lara-Sánchez, Antonio Rodríguez-Diéguez, Alexandr Shafir, Alberto Ocaña, and Carlos Alonso-Moreno. "Tuning the Cytotoxicity of Bis-Phosphino-Amines Ruthenium(II) Para-Cymene Complexes for Clinical Development in Breast Cancer." Pharmaceutics 13, no. 10 (September 26, 2021): 1559. http://dx.doi.org/10.3390/pharmaceutics13101559.
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Despite some limitations such as long-term side effects or the potential presence of intrinsic or acquired resistance, platinum compounds are key therapeutic components for the treatment of several solid tumors. To overcome these limitations, maintaining the same efficacy, organometallic ruthenium(II) compounds have been proposed as a viable alternative to platinum agents as they have a more favorable toxicity profile and represent an ideal template for both, high-throughput and rational drug design. To support the preclinical development of bis-phoshino-amine ruthenium compounds in the treatment of breast cancer, we carried out chemical modifications in the structure of these derivatives with the aim of designing less toxic and more efficient therapeutic agents. We report new bis-phoshino-amine ligands and the synthesis of their ruthenium counterparts. The novel ligands and compounds were fully characterized, water stability analyzed, and their in vitro cytotoxicity against a panel of tumor cell lines representative of different breast cancer subtypes was evaluated. The mechanism of action of the lead compound of the series was explored. In vivo toxicity was also assessed. The results obtained in this article might pave the way for the clinical development of these compounds in breast cancer therapy.
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Boussaad, Ibrahim, Andriana Kotini, Emily K. Dolezal, Stephen Nimer, and Eirini P. Papapetrou. "An iPSC-Based Model Of MDS For Phenotype-Driven Gene and Drug Discovery." Blood 122, no. 21 (November 15, 2013): 859. http://dx.doi.org/10.1182/blood.v122.21.859.859.
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Abstract Despite past and ongoing research efforts, the pathogenetic mechanisms of MDS remain far from understood sufficiently to point to single genes or molecular pathways as putative targets for generation of better mouse models or drug development. In lack of clear targets, the manipulation of disease-associated phenotypes may at present be the best opportunity for disease study and therapeutic intervention. Furthermore, because cellular phenotypes are more proximal to molecular disease mechanisms than phenotypes seen at the level of the tissue or organism (i.e. the murine or human hematopoietic system), they may provide more sensitive and relevant readouts of the disease process. With the advent of patient-specific induced pluripotent stem cells (iPSCs), disease models based on cellular phenotypes (“disease-in-a-dish”) can now be developed and their unique properties promise to revolutionize disease study and drug development. Unlimited cell numbers of biologically relevant cells can be obtained relatively easily and cost-effectively. Here we present a new MDS model based on patient-specific iPSCs and its use in two phenotype-driven screens: (a) a focused genetic screen and (b) a high-throughput chemical screen. We have derived multiple MDS-iPSC lines with deletions of chromosomes 7q or 20q (characteristic chromosomal deletions that we are using as markers of iPSCs derived from the MDS clone) from bone marrow (BM) of 3 patients with MDS and 1 patient with sAML. We also derived isogenic karyotypically normal iPSC lines in parallel from the same BM samples. We identified two cellular phenotypes specific to the MDS-iPSCs: decreased proliferation rate and decreased potential for pan-hematopoietic differentiation and reduced clonogenic capacity of their hematopoietic progeny. These phenotypes are consistent across multiple iPSC lines from different patients and absent from their isogenic normal iPSC controls. They are reminiscent of the behavior of ex vivo cultured primary MDS BM cells and are therefore likely to be relevant to the disease process. Furthermore, they are rescued by spontaneous compensation for chr7q dosage through acquisition of an extra chr7 and recapitulated by the engineering of artificial chr7q deletions in normal iPSCs. To identify critical MDS gene(s) on chr7q, we performed a screen of 62 candidate haploinsufficient genes (with reduced expression by at least 1.5-fold in our del(7q)-iPSCs compared to their isogenic normal iPSCs) for rescue of the proliferation and/or hematopoietic differentiation phenotype. We constructed a lentiviral library of all candidate ORFs (and 14 additional alternative transcripts) linked to eGFP through a P2A peptide and each tagged with a unique 4-nt barcode sequence to its 3’ UTR. The library was packaged as a pool and transduced into two different del(7q)-iPSC lines. The cells were passaged for 16 weeks and gDNA was isolated every 2 weeks. In parallel, the cells were differentiated along the hematopoietic lineage and gDNA was isolated from CD45+ cells FACS-sorted on day 15 of differentiation. High-throughput sequencing of the barcodes identified 5 ORFs that became enriched in undifferentiated iPSCs over time (rescue of proliferation) and 4 ORFs enriched in sorted CD45+hematopoietic progenitors (rescue of hematopoietic differentiation), 2 of which overlapped. All 9 hits are being further validated in more focused screens. Second, we used the same platform for a high-throughput small molecule screen. We optimized the plating conditions and densities for a 384-well format using a luminescent cell viability assay and conducted a screen of 2000 compounds comprising known drugs, natural products, and other bioactives and chemicals, in an MDS-iPSC line (2.13) and its isogenic normal control (2.8). Primary hits were defined as compounds that enhanced the growth of the MDS-iPSC line, but not of the control normal iPSC line in a compound dose-dependent manner. 38 primary hits were retested in a dose-response survival assay in one additional MDS- (2.A1-3), one additional isogenic normal iPSC line (2.12) and one sAML iPSC line over 8 concentrations and 12 compounds were prioritized for further studies. Our data highlight the potential of this new iPSC-based model of MDS for screens to identify genes or compounds that affect cellular phenotypes by acting on previously undefined targets. Disclosures: No relevant conflicts of interest to declare.
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Turkson, James, Shumin Zhang, Jay Palmer, Heidi Kay, Joseph Stanko, Linda B. Mora, Said Sebti, Hua Yu, and Richard Jove. "Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity." Molecular Cancer Therapeutics 3, no. 12 (December 1, 2004): 1533–42. http://dx.doi.org/10.1158/1535-7163.1533.3.12.
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Abstract DNA-alkylating agents that are platinum complexes induce apoptotic responses and have wide application in cancer therapy. The potential for platinum compounds to modulate signal transduction events that contribute to their therapeutic outcome has not been extensively examined. Among the signal transducer and activator of transcription (STAT) proteins, Stat3 activity is frequently up-regulated in many human tumors. Various lines of evidence have established a causal role for aberrant Stat3 activity in malignant transformation and provided validation for its targeting in the development of small-molecule inhibitors as novel cancer therapeutics. We report here that platinum-containing compounds disrupt Stat3 signaling and suppress its biological functions. The novel platinum (IV) compounds, CPA-1, CPA-7, and platinum (IV) tetrachloride block Stat3 activity in vitro at low micromolar concentrations. In malignant cells that harbor constitutively activated Stat3, CPA-1, CPA-7, and platinum (IV) tetrachloride inhibit cell growth and induce apoptosis in a manner that reflects the attenuation of persistent Stat3 activity. By contrast, cells that do not contain persistent Stat3 activity are marginally affected or are not affected by these compounds. Moreover, CPA-7 induces the regression of mouse CT26 colon tumor, which correlates with the abrogation of persistent Stat3 activity in tumors. Thus, the modulation of oncogenic signal transduction pathways, such as Stat3, may be one of the key molecular mechanisms for the antitumor effects of platinum (IV)–containing complexes.
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Romano, Alberto, Michele Antonio Capozza, Stefano Mastrangelo, Palma Maurizi, Silvia Triarico, Rolando Rolesi, Giorgio Attinà, Anna Rita Fetoni, and Antonio Ruggiero. "Assessment and Management of Platinum-Related Ototoxicity in Children Treated for Cancer." Cancers 12, no. 5 (May 17, 2020): 1266. http://dx.doi.org/10.3390/cancers12051266.
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Platinum compounds are a group of chemotherapeutic agents included in many pediatric and adult oncologic treatment protocols. The main platinum compounds are cisplatin, carboplatin, and oxaliplatin. Their use in clinical practice has greatly improved long-term survival of pediatric patients, but they also cause some toxic effects: ototoxicity, myelosuppression, nephrotoxicity, and neurotoxicity. Hearing damage is one of the main toxic effects of platinum compounds, and it derives from the degeneration of hair cells of the ear, which, not having self-renewal capacity, cannot reconstitute themselves. Hearing loss from platinum exposure is typically bilateral, sensorineural, and permanent, and it is caused by the same mechanisms with which platinum acts on neoplastic cells. According to available data from the literature, the optimal timing for the audiological test during and after treatment with platinum compounds is not well defined. Moreover, no substances capable of preventing the onset of hearing loss have been identified.
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Ali, Mayyadah Mahmood, and Tavga Ahmed Aziz. "Toxic Effect of Platinum Compounds: Molecular Mechanisms of Toxicity." Al-Rafidain Journal of Medical Sciences ( ISSN: 2789-3219 ) 1 (October 30, 2021): 81–88. http://dx.doi.org/10.54133/ajms.v1i.32.
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Despite their effectiveness as a crucial component of combination chemotherapy regimens against solid tumors, platinum compounds have many serious side effects that limit their use. This review article focuses on the various toxic effects of platinum compounds in cancer patients and the mechanisms of toxicity associated with each of these toxic effects. It also describes the future directions for developing novel platinum compounds, using both animal and human studies. The reference lists of relevant publications were included after searching the Google and Google Scholar databases, PubMed, and scientific journals. It focuses primarily on trials that were published between 2005 and 2020. Platinum-based medicines, as a soft nucleophile, can freely bind to peptides and proteins containing sulfur residues from thiol-containing amino acids like cysteine and methionine, as well as the antioxidant peptide glutathione. Platinum medicines, on the other hand, are primarily directed at nuclear DNA. Platinum medicines bind to normal cells as well as malignant cells, particularly those in fast growing tissues, causing a variety of dangerous side effects. Fast-growing tissues such as the mucous membranes of the mouth, throat, stomach, and intestines, bone marrow, and hair follicles can be damaged by cytotoxic chemotherapy drugs, resulting in gastrointestinal toxicities, myelosuppression, and hair loss. Platinum compounds also cause nephrotoxicity and hepatotoxicity, which are well-known side effects. Current platinum-based chemotherapy treatments have been restricted in the last decade, prompting a search for novel platinum-based medications with mechanisms of action distinct from those of existing chemotherapeutics.
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Adokoh, Christian K. "Therapeutic potential of dithiocarbamate supported gold compounds." RSC Advances 10, no. 5 (2020): 2975–88. http://dx.doi.org/10.1039/c9ra09682e.
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Samochocka, K., and M. Czauderna. "Use of INAA to study the biodistribution of platinum compounds in animals." Journal of Radioanalytical and Nuclear Chemistry Letters 106, no. 3 (August 1986): 153–57. http://dx.doi.org/10.1007/bf02166785.
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Kushner, Brian H., Amy Budnick, Kim Kramer, Shakeel Modak, and Nai-Kong V. Cheung. "Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma." Cancer 107, no. 2 (2006): 417–22. http://dx.doi.org/10.1002/cncr.22004.
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Herman, Terence S., Beverly A. Teicher, Lynn Van Ummersen, and Laura S. Collins. "Synthesis and testing of new platinum-based compounds for use with hyperthermia." International Journal of Radiation Oncology*Biology*Physics 13 (October 1987): 165–66. http://dx.doi.org/10.1016/0360-3016(87)91161-8.
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Charignon, Elsa, Mathilde Bouché, Caroline Clave-Darcissac, Georges Dahm, Gabriel Ichim, Anthony Clotagatide, Hichem C. Mertani, et al. "In Cellulo Evaluation of the Therapeutic Potential of NHC Platinum Compounds in Metastatic Cutaneous Melanoma." International Journal of Molecular Sciences 21, no. 21 (October 22, 2020): 7826. http://dx.doi.org/10.3390/ijms21217826.
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We describe here the evaluation of the cytotoxic efficacy of two platinum (II) complexes bearing an N-heterocyclic carbene (NHC) ligand, a pyridine ligand and bromide or iodide ligands on a panel of human metastatic cutaneous melanoma cell lines representing different genetic subsets including BRAF-inhibitor-resistant cell lines, namely A375, SK-MEL-28, MeWo, HMCB, A375-R, SK-MEL-5-R and 501MEL-R. Cisplatin and dacarbazine were also studied for comparison purposes. Remarkably, the iodine-labelled Pt-NHC complex strongly inhibited proliferation of all tested melanoma cells after 1-h exposure, likely due to its rapid uptake by melanoma cells. The mechanism of this inhibitory activity involves the formation of DNA double-strand breaks and apoptosis. Considering the intrinsic chemoresistance of metastatic melanoma cells of current systemic treatments, these findings are promising and could give research opportunities in the future to improve the prognosis of patients suffering from unresectable metastatic melanoma that are not eligible or that do not respond to the most effective drugs available to date, namely BRAF inhibitors and the anti-PD-1 monoclonal antibody (mAb).
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Schweer, David, J. Robert McCorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick Ueland, and Jill Kolesar. "Mithramycin and Analogs for Overcoming Cisplatin Resistance in Ovarian Cancer." Biomedicines 9, no. 1 (January 12, 2021): 70. http://dx.doi.org/10.3390/biomedicines9010070.
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Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, in the treatment of platinum-resistant ovarian cancer.
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Lam, Chui, and Kai Chow. "Use of New Therapeutic Compounds in Pregnancy with Renal Disease." Current Women's Health Reviews 1, no. 3 (November 1, 2005): 197–200. http://dx.doi.org/10.2174/157340405774575196.
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Stojic, Isidora, Vladimir Zivkovic, Ivan Srejovic, Nevena Jeremic, Vladimir Jakovljevic, Dragan Djuric, and Slobodan Novokmet. "The Effects of Cisplatin and Its PT(II) Analogue on Oxidative Stress of Isolated Rat Heart/ Efekti Cisplatine I PT(II) Analoga Cisplatine Na Oksidacioni Stres Izolovanog Srca Pacova." Serbian Journal of Experimental and Clinical Research 17, no. 1 (March 1, 2016): 15–20. http://dx.doi.org/10.1515/sjecr-2015-0050.
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Abstract To date, numerous platinum (II) complexes have been successfully used in the treatment of different types of cancer. Therapeutic platinum complexes are different in terms of their structure, chemical reactivity, solubility, pharmacokinetics and toxicity. The aim of our research was the evaluation of cardiotoxicity of dichloro-(ethylendiamine) platinum (II) in a model of isolated rat heart using the Langedorff technique. Oxidative stress was assessed by determination of superoxide anion radical, hydrogen peroxide, Thiobarbituric Acid Reactive Substances and nitric oxide levels from coronary venous effluent. All reagents were perfused at increasing concentrations from 10-8 to 10-4 M for 30 minutes. In this paper, we report that substances administered at higher doses did not induce dose-dependent effects on oxidative stress markers. The results of this research may be of great interest for future studies in this area. There are many novel platinum compounds that had previously demonstrated antitumour activity, and these types of experiments in our study can assist in the examination of their cardiotoxicity. These results could be helpful for understanding dose-dependent side effects of existing and novel platinum compounds
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Buyana, Buhle, Tobeka Naki, Sibusiso Alven, and Blessing Atim Aderibigbe. "Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy." International Journal of Molecular Sciences 23, no. 19 (September 24, 2022): 11261. http://dx.doi.org/10.3390/ijms231911261.
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Colorectal cancer is a common cancer in both men and women. Numerous studies on the therapeutic effectiveness of nanoparticles against colorectal cancer have been reported. Platinum treatments as well as other medications comprising of nanoparticles have been utilized. Drug resistance restricts the use of platinum medicines, despite their considerable efficacy against a variety of cancers. This review reports clinically licensed platinum medicines (cisplatin, carboplatin, and oxaliplatin) combined with various nanoparticles that have been evaluated for their therapeutic efficacy in the treatment of colorectal cancer, including their mechanism of action, resistance, and limitations.
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Dag, Aydan, Manuela Callari, Hongxu Lu, and Martina H. Stenzel. "Modulating the cellular uptake of platinum drugs with glycopolymers." Polymer Chemistry 7, no. 5 (2016): 1031–36. http://dx.doi.org/10.1039/c5py01579k.
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Bernocchi, G., M. G. Bottone, V. M. Piccolini, V. Dal Bo, G. Santin, S. A. De Pascali, D. Migoni, and F. P. Fanizzi. "Developing Central Nervous System and Vulnerability to Platinum Compounds." Chemotherapy Research and Practice 2011 (February 15, 2011): 1–14. http://dx.doi.org/10.1155/2011/315418.
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Comparative studies on the effects of the platinum complexes in use or in clinical trials are carried out in order to discover differences in the neurotoxic potential and the reversibility of neurotoxicity. In this paper, we summarized the current literature on neurotoxicity and chemoresistance of cisplatin (cisPt) and discussed our recent efforts on the interference of cisPt and a new platinum compound [Pt(O,O′-acac)(γ-acac)(DMS)] (PtAcacDMS), with high specific reactivity with sulphur ligands instead of nucleobases as cisPt, on some crucial events of rat postnatal cerebellum development. The acute effects of drug treatments on cell proliferation and death in the external granular layer and granule cell migration and the late effects on the dendrite growth of Purkinje cells were evaluated. Together with the demonstrated antineoplastic effectiveness in vitro, compared with cisPt, data suggest a lower neurotoxicity of PtAcacDMS, in spite of its presence in the brain that involves considerations on the blood brain barrier permeability.
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Villalba, Jose M., Cristina Parrado, Monica Santos-Gonzalez, and Francisco J. Alcain. "Therapeutic use of coenzyme Q10and coenzyme Q10-related compounds and formulations." Expert Opinion on Investigational Drugs 19, no. 4 (March 31, 2010): 535–54. http://dx.doi.org/10.1517/13543781003727495.
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Khokhlova, S. V., M. V. Cherkasova, N. F. Orel, S. V. Limareva, I. Ya Bazaeva, and V. A. Gorbunova. "WHICH PATIENTS WITH OVARIAN CANCER SHOWS THE COMBINATION OF TRABECTEDIN WITH PEGYLATED LIPOSOMAL DOXORUBICIN." Annals of the Russian academy of medical sciences 68, no. 11 (November 12, 2013): 115–21. http://dx.doi.org/10.15690/vramn.v68i11.852.
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Given the high rate of recurrence of ovarian cancer, the search for new therapeutic strategies are topical issue. According to various studies the effectiveness of drug treatment relapse depends on the platinum-free interval, increasing in proportion to its duration. If therapy is platinum-resistant recurrent ovarian cancer is a standard approach, the treatment of platinum-sensitive recurrent algorithm is not fully defined. Comparison of platinum and non-platinum combinations revealed the advantage of combined platinum- treatment for patients with platinum-free interval of more than 6 months without an increase in life expectancy. Non-platinum combination of trabectedin with pegylated liposomal doxorubicin has shown comparable efficacy with an advantage in overall survival in patients with platinum-free interval of 6–12 months. A platinum-free interval prolongation by the use of non-platinum mode increases the efficiency of subsequent platinum-based therapy, increasing the life expectancy of patients . Currently under study molecular markers and prognostic factors allowing to define a group of patients who have the greatest benefit from the use trabectedin with pegylated liposomal doxorubicin as second-line chemotherapy.
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Köberle, Beate, and Sarah Schoch. "Platinum Complexes in Colorectal Cancer and Other Solid Tumors." Cancers 13, no. 9 (April 25, 2021): 2073. http://dx.doi.org/10.3390/cancers13092073.
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Cisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to cisplatin resistance in cancer cells, including reduced drug accumulation, enhanced drug detoxification, modulation of DNA repair mechanisms, and finally alterations in cisplatin DNA damage signaling preventing apoptosis in cancer cells. Regarding colorectal cancer, defects in mismatch repair and altered p53-mediated DNA damage signaling are the main factors controlling the resistance phenotype. In particular, p53 inactivation appears to be associated with chemoresistance and poor prognosis. To overcome resistance in cancers, several strategies can be envisaged. Improved cisplatin analogues, which retain activity in resistant cancer, might be applied. Targeting p53-mediated DNA damage signaling provides another therapeutic strategy to circumvent cisplatin resistance. This review provides an overview on the DNA repair pathways involved in the processing of cisplatin damage and will describe signal transduction from cisplatin DNA lesions, with special attention given to colorectal cancer cells. Furthermore, examples for improved platinum compounds and biochemical modulators of cisplatin DNA damage signaling will be presented in the context of colon cancer therapy.
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Ronchi, Cristina L., Silviu Sbiera, Luitgard Kraus, Sebastian Wortmann, Sarah Johanssen, Patrick Adam, Holger S. Willenberg, Stefanie Hahner, Bruno Allolio, and Martin Fassnacht. "Expression of excision repair cross complementing group 1 and prognosis in adrenocortical carcinoma patients treated with platinum-based chemotherapy." Endocrine-Related Cancer 16, no. 3 (September 2009): 907–18. http://dx.doi.org/10.1677/erc-08-0224.
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Therapeutic progress in adrenocortical carcinoma (ACC) is severely hampered by its low incidence. Platinum-based chemotherapies are the most effective cytotoxic treatment regimens in ACC but response rates remain <50%. In other tumor entities, expression of excision repair cross complementing group 1 (ERCC1) predicts resistance to platinum compounds. Therefore, we correlated ERCC1 protein expression and clinical outcome. We have retrolectively established adrenal tissue microarrays and analyzed prospectively samples from 163 ACCs, 15 benign adrenal adenomas, and 8 normal adrenal glands by immunohistochemistry for ERCC1 protein expression. Detailed clinical data were available by the German ACC Registry. ERCC1 protein was highly expressed in all normal adrenal glands, 14 benign tumors (93%) and in 75 ACCs (47%). In ACC, no differences in baseline parameters were found between patients with and without ERCC1 expression. Detection of ERCC1 was not correlated with survival in patients who never received platinum-based chemotherapy. In platinum-treated patients (n=45), objective response to platinum compounds was observed in 3/21 patients (14.3%) with high ERCC1 expression and in 7/24 patients (29.2%) with low ERCC1 expression (P=0.23). ERCC1 expression was strongly correlated with overall survival after platinum treatment (median: eight months in patients with high ERCC1 versus 24 months in low ERCC1 expression, hazard ratio (HR) 2.95 (95% confidence interval (CI) 1.4–6.2), P=0.004). Multivariate analysis confirmed that high ERCC1 expression was a predictive factor for poor prognosis in platinum treated patients (HR 2.2, 95% CI 1.0–4.5, P=0.038). Our findings suggest that ERCC1 expression is the first factor for predicting survival in ACC patients treated with platinum-based chemotherapy.
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Soejima, Takashi, Jun-ichi Minami, Jin-zhong Xiao, and Fumiaki Abe. "Innovative use of platinum compounds to selectively detect live microorganisms by polymerase chain reaction." Biotechnology and Bioengineering 113, no. 2 (August 19, 2015): 301–10. http://dx.doi.org/10.1002/bit.25711.
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Szefler, Beata, Przemysław Czeleń, and Przemysław Krawczyk. "The Affinity of Carboplatin to B-Vitamins and Nucleobases." International Journal of Molecular Sciences 22, no. 7 (March 31, 2021): 3634. http://dx.doi.org/10.3390/ijms22073634.
Full textAbstract:
Platinum compounds have found wide application in the treatment of various types of cancer and carboplatin is one of the main platinum-based drugs used as antitumor agents. The anticancer activity of carboplatin arises from interacting with DNA and inducing programmed cell death. However, such interactions may occur with other chemical compounds, such as vitamins containing aromatic rings with lone-pair orbitals, which reduces the anti-cancer effect of carboplatin. The most important aspect of the conducted research was related to the evaluation of carboplatin affinity to vitamins from the B group and the potential impact of such interactions on the reduction of therapeutic capabilities of carboplatin in anticancer therapy. Realized computations, including estimation of Gibbs Free Energies, allowed for the identification of the most reactive molecule, namely vitamin B6 (pyridoxal phosphate). In this case, the computational estimations indicating carboplatin reactivity were confirmed by spectrophotometric measurements.
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Venturella, Giuseppe, Valeria Ferraro, Fortunato Cirlincione, and Maria Letizia Gargano. "Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials." International Journal of Molecular Sciences 22, no. 2 (January 10, 2021): 634. http://dx.doi.org/10.3390/ijms22020634.
Full textAbstract:
Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.
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Venturella, Giuseppe, Valeria Ferraro, Fortunato Cirlincione, and Maria Letizia Gargano. "Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials." International Journal of Molecular Sciences 22, no. 2 (January 10, 2021): 634. http://dx.doi.org/10.3390/ijms22020634.
Full textAbstract:
Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.
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Shoji, Eto, Sato, Soma, Fukagawa, Tomabechi, Takatori, et al. "A New Therapeutic Strategy for Recurrent Ovarian Cancer―Bevacizumab beyond Progressive Disease." Healthcare 7, no. 3 (September 19, 2019): 109. http://dx.doi.org/10.3390/healthcare7030109.
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Treatment beyond progressive disease (PD) is a concept that even after drugs become ineffective, their continued use is more beneficial for patients than their discontinuation. In recent years, a concept of bevacizumab beyond PD (BBP) has attracted attention in the treatment of various cancers, and the usefulness of this concept has been evaluated. BBP has been proven to prolong overall survival (OS) in recurrent colorectal cancer and progression-free survival (PFS) in recurrent breast and lung cancers. With regard to the treatment of ovarian cancer, the MITO16/MaNGO-OV2B study (the Multicenter Phase III Randomized Study with Second Line Chemotherapy Plus or Minus Bevacizumab in Patients with Platinum Sensitive Epithelial Ovarian Cancer Recurrence After a Bevacizumab/Chemotherapy First Line) was conducted in patients with platinum-sensitive recurrence and the JGOG3023 study (the Open-Label, Randomized, Phase II Trial Evaluating the Efficacy and Safety of Standard of Care with or Without Bevacizumab in Platinum-Resistant Ovarian Cancer Patients Previously Treated with Bevacizumab for Front-Line or Platinum-Sensitive Ovarian Cancer) was conducted in patients with platinum-resistant recurrence. The MITO16/MaNGO-OV2B study, reported in the 2018 annual meeting of the American Society of Clinical Oncology, showed that BBP achieved prolonged PFS. In the JGOG3023 study, enrollment of patients was completed in December 2018, and the follow-up period has been initiated. Proving the effectiveness of BBP in the treatment of ovarian cancer may provide a new therapeutic strategy and contribute to improved treatment outcomes in patients with poor prognosis and limited therapeutic options.