Artykuły w czasopismach: „Preclinical oncology”

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Kahn, Jenna, Philip J. Tofilon i Kevin Camphausen. "Preclinical models in radiation oncology". Radiation Oncology 7, nr 1 (2012): 223. http://dx.doi.org/10.1186/1748-717x-7-223.

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Kumari, Rajendra. "Refining Preclinical Modeling in Oncology". Genetic Engineering & Biotechnology News 33, nr 19 (listopad 2013): 34–35. http://dx.doi.org/10.1089/gen.33.19.14.

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Ibarrola-Villava, Maider, Andrés Cervantes i Alberto Bardelli. "Preclinical models for precision oncology". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1870, nr 2 (grudzień 2018): 239–46. http://dx.doi.org/10.1016/j.bbcan.2018.06.004.

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Gardner, Eric E., i Charles M. Rudin. "Preclinical oncology — reporting transparency needed". Nature Reviews Clinical Oncology 13, nr 1 (15.12.2015): 8–9. http://dx.doi.org/10.1038/nrclinonc.2015.216.

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Clézardin, Philippe, Ismahène Benzaïd i Peter I. Croucher. "Bisphosphonates in preclinical bone oncology". Bone 49, nr 1 (lipiec 2011): 66–70. http://dx.doi.org/10.1016/j.bone.2010.11.017.

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Thöni, C. "Preclinical research in oncology: Gender aspects". memo - Magazine of European Medical Oncology 4, nr 4 (grudzień 2011): 217–20. http://dx.doi.org/10.1007/s12254-011-0295-y.

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BOULEFTOUR, WAFA, BENOITE MERY, ELISE ROWINSKI, CHARLENE RIVIER, ELISABETH DAGUENET i NICOLAS MAGNE. "Cardio-Oncology Preclinical Models: A Comprehensive Review". Anticancer Research 41, nr 11 (listopad 2021): 5355–64. http://dx.doi.org/10.21873/anticanres.15348.

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Wittenburg, Luke A., i Daniel L. Gustafson. "Optimizing preclinical study design in oncology research". Chemico-Biological Interactions 190, nr 2-3 (kwiecień 2011): 73–78. http://dx.doi.org/10.1016/j.cbi.2011.01.029.

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Zumberg, Marc S., Virginia C. Broudy, Elizabeth M. Bengtson i Scott D. Gitlin. "Preclinical Medical Student Hematology/Oncology Education Environment". Journal of Cancer Education 30, nr 4 (31.01.2015): 711–18. http://dx.doi.org/10.1007/s13187-014-0778-8.

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Hormuth, David A., Anna G. Sorace, John Virostko, Richard G. Abramson, Zaver M. Bhujwalla, Pedro Enriquez‐Navas, Robert Gillies i in. "Translating preclinical MRI methods to clinical oncology". Journal of Magnetic Resonance Imaging 50, nr 5 (29.03.2019): 1377–92. http://dx.doi.org/10.1002/jmri.26731.

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Patel, Tulsi Dipakbhai, Gunjan i Venkata Gangadhar Vanteddu. "Bio-markers of immuno-oncology". Journal of Pharmaceutical and Biological Sciences 11, nr 2 (15.02.2024): 105–11. http://dx.doi.org/10.18231/j.jpbs.2023.017.

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Since its inception until the rapid advancements, the immuno-oncology (I-O) landscape has undergone significant modifications. Thousands of possible I-O medicines and therapy combinations are being tested in clinical trials as part of the current drug development pipeline. Suppose these assets are to be developed effectively and successfully. In that case, it is necessary to invest in and use the proper techniques and technology to speed up the transition from preclinical evaluation to clinical development. These tools, which include suitable preclinical models, pharmacodynamics-related biomarkers, prediction and monitoring capabilities, and developing clinical trial designs, enable quick and effective evaluation during the development process.The possibility of new findings and insights in each of these three areas to further address the clinical care needs of patients with cancer.These tools include. 1. Appropriate preclinical models, 2. Biomarkers of pharmacodynamics, predictive and monitoring utility, and. 3. Evolving clinical trial designs allow rapid and efficient evaluation during the development process.This article provides an overview of how novel discoveries and insights into each of these three areas have the potential further to address the clinical management needs of patients with cancer.

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Holmen Olofsson, Gitte, Agnete Witness Praest Jensen, Manja Idorn i Per thor Straten. "Exercise Oncology and Immuno-Oncology; A (Future) Dynamic Duo". International Journal of Molecular Sciences 21, nr 11 (27.05.2020): 3816. http://dx.doi.org/10.3390/ijms21113816.

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Recent advances in clinical oncology is based on exploiting the capacity of the immune system to combat cancer: immuno-oncology. Thus, immunotherapy of cancer is now used to treat a variety of malignant diseases. A striking feature is that even patients with late-stage disease may experience curative responses. However, most patients still succumb to disease, and do not benefit from treatment. Exercise has gained attention in clinical oncology and has been used for many years to improve quality of life, as well as to counteract chemotherapy-related complications. However, more recently, exercise has garnered interest, largely due to data from animal studies suggesting a striking therapeutic effect in preclinical cancer models; an effect largely mediated by the immune system. In humans, physical activity is associated with a lower risk for a variety of malignancies, and some data suggest a positive clinical effect for cancer patients. Exercise leads to mobilization of cells of the immune system, resulting in redistribution to different body compartments, and in preclinical models, exercise has been shown to lead to immunological changes in the tumor microenvironment. This suggests that exercise and immunotherapy could have a synergistic effect if combined.

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Wang, Yufei, Sarah E. Shelton, Gabriella Kastrunes, David A. Barbie, Gordon J. Freeman i Wayne A. Marasco. "Preclinical models for development of immune–oncology therapies". Immuno Oncology Insights 03, nr 08 (3.10.2022): 396–98. http://dx.doi.org/10.18609/ioi.2022.41.

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van Bekkum, Dirk W. "Preclinical experiments". Best Practice & Research Clinical Haematology 17, nr 2 (czerwiec 2004): 201–22. http://dx.doi.org/10.1016/j.beha.2004.04.003.

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Fiordelisi, Maria Felicia, Carlo Cavaliere, Luigi Auletta, Luca Basso i Marco Salvatore. "Magnetic Resonance Imaging for Translational Research in Oncology". Journal of Clinical Medicine 8, nr 11 (6.11.2019): 1883. http://dx.doi.org/10.3390/jcm8111883.

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The translation of results from the preclinical to the clinical setting is often anything other than straightforward. Indeed, ideas and even very intriguing results obtained at all levels of preclinical research, i.e., in vitro, on animal models, or even in clinical trials, often require much effort to validate, and sometimes, even useful data are lost or are demonstrated to be inapplicable in the clinic. In vivo, small-animal, preclinical imaging uses almost the same technologies in terms of hardware and software settings as for human patients, and hence, might result in a more rapid translation. In this perspective, magnetic resonance imaging might be the most translatable technique, since only in rare cases does it require the use of contrast agents, and when not, sequences developed in the lab can be readily applied to patients, thanks to their non-invasiveness. The wide range of sequences can give much useful information on the anatomy and pathophysiology of oncologic lesions in different body districts. This review aims to underline the versatility of this imaging technique and its various approaches, reporting the latest preclinical studies on thyroid, breast, and prostate cancers, both on small laboratory animals and on human patients, according to our previous and ongoing research lines.

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Sitta, Juliana, Pier Paolo Claudio i Candace M. Howard. "Virus-Based Immuno-Oncology Models". Biomedicines 10, nr 6 (18.06.2022): 1441. http://dx.doi.org/10.3390/biomedicines10061441.

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Immunotherapy has been extensively explored in recent years with encouraging results in selected types of cancer. Such success aroused interest in the expansion of such indications, requiring a deep understanding of the complex role of the immune system in carcinogenesis. The definition of hot vs. cold tumors and the role of the tumor microenvironment enlightened the once obscure understanding of low response rates of solid tumors to immune check point inhibitors. Although the major scope found in the literature focuses on the T cell modulation, the innate immune system is also a promising oncolytic tool. The unveiling of the tumor immunosuppressive pathways, lead to the development of combined targeted therapies in an attempt to increase immune infiltration capability. Oncolytic viruses have been explored in different scenarios, in combination with various chemotherapeutic drugs and, more recently, with immune check point inhibitors. Moreover, oncolytic viruses may be engineered to express tumor specific pro-inflammatory cytokines, antibodies, and antigens to enhance immunologic response or block immunosuppressive mechanisms. Development of preclinical models capable to replicate the human immunologic response is one of the major challenges faced by these studies. A thorough understanding of immunotherapy and oncolytic viruses’ mechanics is paramount to develop reliable preclinical models with higher chances of successful clinical therapy application. Thus, in this article, we review current concepts in cancer immunotherapy including the inherent and synthetic mechanisms of immunologic enhancement utilizing oncolytic viruses, immune targeting, and available preclinical animal models, their advantages, and limitations.

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Franklin, Maryland Rosenfeld, Suso Platero, Kamal S. Saini, Giuseppe Curigliano i Steven Anderson. "Immuno-oncology trends: preclinical models, biomarkers, and clinical development". Journal for ImmunoTherapy of Cancer 10, nr 1 (styczeń 2022): e003231. http://dx.doi.org/10.1136/jitc-2021-003231.

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The landscape in immuno-oncology (I-O) has undergone profound changes since its early beginnings up through the rapid advances happening today. The current drug development pipeline consists of thousands of potential I-O therapies and therapy combinations, many of which are being evaluated in clinical trials. The efficient and successful development of these assets requires the investment in and utilization of appropriate tools and technologies that can facilitate the rapid transitions from preclinical evaluation through clinical development. These tools include (i) appropriate preclinical models, (ii) biomarkers of pharmacodynamic, predictive and monitoring utility, and (iii) evolving clinical trial designs that allow rapid and efficient evaluation during the development process. This article provides an overview of how novel discoveries and insights into each of these three areas have the potential to further address the clinical management needs for patients with cancer.

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Chen, Stephen R., Frederick F. Lang i Peter Kan. "Preclinical animal brain tumor models for interventional neuro-oncology". Journal of NeuroInterventional Surgery 14, nr 5 (12.04.2022): neurintsurg—2022–018968. http://dx.doi.org/10.1136/neurintsurg-2022-018968.

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Tamm, Ingo, i Mandy Wagner. "Antisense Therapy in Clinical Oncology: Preclinical and Clinical Experiences". Molecular Biotechnology 33, nr 3 (2006): 221–38. http://dx.doi.org/10.1385/mb:33:3:221.

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Oertel, Michael, Martina Schmitz, Jan Carl Becker, Hans Theodor Eich i Anna Schober. "Successful integration of radiation oncology in preclinical medical education". Strahlentherapie und Onkologie 195, nr 12 (15.07.2019): 1104–9. http://dx.doi.org/10.1007/s00066-019-01492-z.

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Wulf-Goldenberg, A., M. Stecklum, Z. Reiner, I. Fichtner i J. Hoffmann. "Mouse models for translational preclinical research in immuno-oncology". European Journal of Cancer 69 (grudzień 2016): S53—S54. http://dx.doi.org/10.1016/s0959-8049(16)32746-0.

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Barachini, Serena, Mariangela Morelli, Orazio Santo Santonocito i Chiara Maria Mazzanti. "Preclinical glioma models in neuro-oncology: enhancing translational research". Current Opinion in Oncology 35, nr 6 (1.09.2023): 536–42. http://dx.doi.org/10.1097/cco.0000000000000997.

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Purpose of review Gliomas represent approximately 25% of all primary brain and other central nervous system (CNS) tumors and 81% of malignant tumors. Unfortunately, standard treatment approaches for most CNS cancers have shown limited improvement in patient survival rates. Recent findings The current drug development process has been plagued by high failure rates, leading to a shift towards human disease models in biomedical research. Unfortunately, suitable preclinical models for brain tumors have been lacking, hampering our understanding of tumor initiation processes and the discovery of effective treatments. In this review, we will explore the diverse preclinical models employed in neuro-oncology research and their contributions to translational science. Summary By utilizing a combination of these preclinical models and fostering interdisciplinary collaborations, researchers can deepen their understanding of glioma brain tumors and develop novel therapeutic strategies to combat these devastating diseases. These models offer promising prospects for personalized and efficacious treatments for these challenging malignancies. Although it is unrealistic to fully replicate the complexity of the human body in vitro, the ultimate goal should be to achieve the closest possible resemblance to the clinical context.

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Green, Jonathan R. "Bisphosphonates: Preclinical Review". Oncologist 9, S4 (wrzesień 2004): 3–13. http://dx.doi.org/10.1634/theoncologist.9-90004-3.

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Fletcher, Nicholas, Aditya Ardana i Kristofer J. Thurecht. "Preclinical Imaging of siRNA Delivery". Australian Journal of Chemistry 69, nr 10 (2016): 1073. http://dx.doi.org/10.1071/ch16079.

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Small interfering RNA (siRNA) is emerging as a class of therapeutic with extremely high potential, particularly in the field of oncology. Despite this growing interest, further understanding of how siRNA behaves in vivo is still required before significant uptake into clinical application. To this end, many molecular imaging modalities have been utilised to gain a better understanding of the biodistribution and pharmacokinetics of administered siRNA and delivery vehicles. This highlight aims to provide an overview of the current state of the field for preclinical imaging of siRNA delivery.

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Vanhaezebrouck, Isabelle F., i Matthew L. Scarpelli. "Companion Animals as a Key to Success for Translating Radiation Therapy Research into the Clinic". Cancers 15, nr 13 (27.06.2023): 3377. http://dx.doi.org/10.3390/cancers15133377.

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Many successful preclinical findings fail to be replicated during translation to human studies. This leads to significant resources being spent on large clinical trials, and in some cases, promising therapeutics not being pursued due to the high costs of clinical translation. These translational failures emphasize the need for improved preclinical models of human cancer so that there is a higher probability of successful clinical translation. Companion-animal cancers offer a potential solution. These cancers are more similar to human cancer than other preclinical models, with a natural evolution over time, genetic alterations, intact immune system, and a permanent adaptation to the microenvironment. These advantages have led pioneers in veterinary radiation oncology to aid human medicine by elucidating basic principles of radiation biology. More recently, the veterinary and human radiation oncology fields have increasingly collaborated to achieve advancements in education, radiotherapy techniques, and trial networks. This review describes these advancements, including significant prior research findings and the evolution of the veterinary radiation oncology discipline. It concludes by describing how companion-animal models can help shape the future of human radiotherapy. Taken as a whole, this review suggests companion-animal cancers may become widely used for preclinical radiotherapy research.

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Fosse, Vibeke, Emanuela Oldoni, Chiara Gerardi, Rita Banzi, Maddalena Fratelli, Florence Bietrix, Anton Ussi, Antonio L. Andreu i Emmet McCormack. "Evaluating Translational Methods for Personalized Medicine—A Scoping Review". Journal of Personalized Medicine 12, nr 7 (19.07.2022): 1177. http://dx.doi.org/10.3390/jpm12071177.

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The introduction of personalized medicine, through the increasing multi-omics characterization of disease, brings new challenges to disease modeling. The scope of this review was a broad evaluation of the relevance, validity, and predictive value of the current preclinical methodologies applied in stratified medicine approaches. Two case models were chosen: oncology and brain disorders. We conducted a scoping review, following the Joanna Briggs Institute guidelines, and searched PubMed, EMBASE, and relevant databases for reports describing preclinical models applied in personalized medicine approaches. A total of 1292 and 1516 records were identified from the oncology and brain disorders search, respectively. Quantitative and qualitative synthesis was performed on a final total of 63 oncology and 94 brain disorder studies. The complexity of personalized approaches highlights the need for more sophisticated biological systems to assess the integrated mechanisms of response. Despite the progress in developing innovative and complex preclinical model systems, the currently available methods need to be further developed and validated before their potential in personalized medicine endeavors can be realized. More importantly, we identified underlying gaps in preclinical research relating to the relevance of experimental models, quality assessment practices, reporting, regulation, and a gap between preclinical and clinical research. To achieve a broad implementation of predictive translational models in personalized medicine, these fundamental deficits must be addressed.

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Stewart, Elizabeth, i Burgess Freeman. "YIA20-006: Preclinical Pediatric MATCH". Journal of the National Comprehensive Cancer Network 18, nr 3.5 (20.03.2020): YIA20–006. http://dx.doi.org/10.6004/jnccn.2019.7485.

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Pugh, Trevor J., i Benjamin Haibe-Kains. "REFLECTions on Combination Therapies Empowered by Data Sharing". Cancer Discovery 12, nr 6 (2.06.2022): 1416–18. http://dx.doi.org/10.1158/2159-8290.cd-22-0330.

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Summary: Li and colleagues present REFLECT, a computational approach to precision oncology that nominates effective drug combinations by utilizing a diverse compendium of publicly available preclinical and clinical genomic, transcriptomic, and proteomic data. The preliminary validation of the REFLECT system in preclinical and clinical trial settings showcases potential for clinical implementation, although challenges remain. See related article by Li et al., p. 1542 (4).

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van Rijt, Antonia, Evan Stefanek i Karolina Valente. "Preclinical Testing Techniques: Paving the Way for New Oncology Screening Approaches". Cancers 15, nr 18 (7.09.2023): 4466. http://dx.doi.org/10.3390/cancers15184466.

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Prior to clinical trials, preclinical testing of oncology drug candidates is performed by evaluating drug candidates with in vitro and in vivo platforms. For in vivo testing, animal models are used to evaluate the toxicity and efficacy of drug candidates. However, animal models often display poor translational results as many drugs that pass preclinical testing fail when tested with humans, with oncology drugs exhibiting especially poor acceptance rates. The FDA Modernization Act 2.0 promotes alternative preclinical testing techniques, presenting the opportunity to use higher complexity in vitro models as an alternative to in vivo testing, including three-dimensional (3D) cell culture models. Three-dimensional tissue cultures address many of the shortcomings of 2D cultures by more closely replicating the tumour microenvironment through a combination of physiologically relevant drug diffusion, paracrine signalling, cellular phenotype, and vascularization that can better mimic native human tissue. This review will discuss the common forms of 3D cell culture, including cell spheroids, organoids, organs-on-a-chip, and 3D bioprinted tissues. Their advantages and limitations will be presented, aiming to discuss the use of these 3D models to accurately represent human tissue and as an alternative to animal testing. The use of 3D culture platforms for preclinical drug development is expected to accelerate as these platforms continue to improve in complexity, reliability, and translational predictivity.

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Valluru, Keerthi S., Katheryne E. Wilson i Jürgen K. Willmann. "Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience". Radiology 280, nr 2 (sierpień 2016): 332–49. http://dx.doi.org/10.1148/radiol.16151414.

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Hasmann, Max, Benno Rattel i Roland Löser. "Preclinical data for Droloxifene". Cancer Letters 84, nr 2 (wrzesień 1994): 101–16. http://dx.doi.org/10.1016/0304-3835(94)90364-6.

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Dholakia, Jhalak, Carly Scalise i Rebecca C. Arend. "Assessing Preclinical Research Models for Immunotherapy for Gynecologic Malignancies". Cancers 13, nr 7 (2.04.2021): 1694. http://dx.doi.org/10.3390/cancers13071694.

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Gynecologic malignancies are increasing in incidence, with a plateau in clinical outcomes necessitating novel treatment options. Immunotherapy and modulation of the tumor microenvironment are rapidly developing fields of interest in gynecologic oncology translational research; examples include the PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) axes and the Wnt pathway. However, clinical successes with these agents have been modest and lag behind immunotherapy successes in other malignancies. A thorough contextualization of preclinical models utilized in gynecologic oncology immunotherapy research is necessary in order to effectively and efficiently develop translational medicine. These include murine models, in vitro assays, and three-dimensional human-tissue-based systems. Here, we provide a comprehensive review of preclinical models for immunotherapy in gynecologic malignancies, including benefits and limitations of each, in order to inform study design and translational research models. Improved model design and implementation will optimize preclinical research efficiency and increase the translational value to positive findings, facilitating novel treatments that improve patient outcomes.

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Liu, Jinsha, Priyanka Pandya i Sepideh Afshar. "Therapeutic Advances in Oncology". International Journal of Molecular Sciences 22, nr 4 (18.02.2021): 2008. http://dx.doi.org/10.3390/ijms22042008.

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Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment options in oncology, and an in-depth discussion of the therapeutics in the preclinical stage for the treatment of breast cancer, lung cancer, and multiple myeloma.

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Green, Jonathan R. "Preclinical pharmacology of zoledronic acid". Seminars in Oncology 29, nr 6 Suppl 21 (grudzień 2002): 3–11. http://dx.doi.org/10.1053/sonc.2002.37421.

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MUNDY, G. "Preclinical models of bone metastases". Seminars in Oncology 28 (sierpień 2001): 2–8. http://dx.doi.org/10.1016/s0093-7754(01)90225-8.

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AKITA, R., i M. SLIWKOWSKI. "Preclinical studies with Erlotinib (Tarceva)". Seminars in Oncology 30, nr 3 (czerwiec 2003): 15–24. http://dx.doi.org/10.1016/s0093-7754(03)70011-6.

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Kim, Minlee, Andrea L. Kasinski i Frank J. Slack. "MicroRNA therapeutics in preclinical cancer models". Lancet Oncology 12, nr 4 (kwiecień 2011): 319–21. http://dx.doi.org/10.1016/s1470-2045(11)70067-5.

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Duncan, R., L. W. Seymour, K. Ulbrich, F. Spreafico, M. Grandi, M. Ripamonti, M. Farao i A. Suarato. "Preclinical evaluation of polymer-bound doxorubicin". European Journal of Cancer and Clinical Oncology 27 (styczeń 1991): S52. http://dx.doi.org/10.1016/0277-5379(91)91369-t.

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Priester, Marjolein I., Sergio Curto, Gerard C. van Rhoon i Timo L. M. ten Hagen. "External Basic Hyperthermia Devices for Preclinical Studies in Small Animals". Cancers 13, nr 18 (15.09.2021): 4628. http://dx.doi.org/10.3390/cancers13184628.

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Preclinical studies have shown that application of mild hyperthermia (40–43 °C) is a promising adjuvant to solid tumor treatment. To improve preclinical testing, enhance reproducibility, and allow comparison of the obtained results, it is crucial to have standardization of the available methods. Reproducibility of methods in and between research groups on the same techniques is crucial to have a better prediction of the clinical outcome and to improve new treatment strategies (for instance with heat-sensitive nanoparticles). Here we provide a preclinically oriented review on the use and applicability of basic hyperthermia systems available for solid tumor thermal treatment in small animals. The complexity of these techniques ranges from a simple, low-cost water bath approach, irradiation with light or lasers, to advanced ultrasound and capacitive heating devices.

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Dasgupta, Pushan, Veerakumar Balasubramanyian, John F. de Groot i Nazanin K. Majd. "Preclinical Models of Low-Grade Gliomas". Cancers 15, nr 3 (18.01.2023): 596. http://dx.doi.org/10.3390/cancers15030596.

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Diffuse infiltrating low-grade glioma (LGG) is classified as WHO grade 2 astrocytoma with isocitrate dehydrogenase (IDH) mutation and oligodendroglioma with IDH1 mutation and 1p/19q codeletion. Despite their better prognosis compared with glioblastoma, LGGs invariably recur, leading to disability and premature death. There is an unmet need to discover new therapeutics for LGG, which necessitates preclinical models that closely resemble the human disease. Basic scientific efforts in the field of neuro-oncology are mostly focused on high-grade glioma, due to the ease of maintaining rapidly growing cell cultures and highly reproducible murine tumors. Development of preclinical models of LGG, on the other hand, has been difficult due to the slow-growing nature of these tumors as well as challenges involved in recapitulating the widespread genomic and epigenomic effects of IDH mutation. The most recent WHO classification of CNS tumors emphasizes the importance of the role of IDH mutation in the classification of gliomas, yet there are relatively few IDH-mutant preclinical models available. Here, we review the in vitro and in vivo preclinical models of LGG and discuss the mechanistic challenges involved in generating such models and potential strategies to overcome these hurdles.

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Lau, Joseph, Etienne Rousseau, Daniel Kwon, Kuo-Shyan Lin, François Bénard i Xiaoyuan Chen. "Insight into the Development of PET Radiopharmaceuticals for Oncology". Cancers 12, nr 5 (21.05.2020): 1312. http://dx.doi.org/10.3390/cancers12051312.

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While the development of positron emission tomography (PET) radiopharmaceuticals closely follows that of traditional drug development, there are several key considerations in the chemical and radiochemical synthesis, preclinical assessment, and clinical translation of PET radiotracers. As such, we outline the fundamentals of radiotracer design, with respect to the selection of an appropriate pharmacophore. These concepts will be reinforced by exemplary cases of PET radiotracer development, both with respect to their preclinical and clinical evaluation. We also provide a guideline for the proper selection of a radionuclide and the appropriate labeling strategy to access a tracer with optimal imaging qualities. Finally, we summarize the methodology of their evaluation in in vitro and animal models and the road to clinical translation. This review is intended to be a primer for newcomers to the field and give insight into the workflow of developing radiopharmaceuticals.

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Gargiulo, Sara, Sandra Albanese i Marcello Mancini. "State-of-the-Art Preclinical Photoacoustic Imaging in Oncology: Recent Advances in Cancer Theranostics". Contrast Media & Molecular Imaging 2019 (30.04.2019): 1–24. http://dx.doi.org/10.1155/2019/5080267.

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The optical imaging plays an increasing role in preclinical studies, particularly in cancer biology. The combined ultrasound and optical imaging, named photoacoustic imaging (PAI), is an emerging hybrid technique for real-time molecular imaging in preclinical research and recently expanding into clinical setting. PAI can be performed using endogenous contrast, particularly from oxygenated and deoxygenated hemoglobin and melanin, or exogenous contrast agents, sometimes targeted for specific biomarkers, providing comprehensive morphofunctional and molecular information on tumor microenvironment. Overall, PAI has revealed notable opportunities to improve knowledge on tumor pathophysiology and on the biological mechanisms underlying therapy. The aim of this review is to introduce the principles of PAI and to provide a brief overview of current PAI applications in preclinical research, highlighting also on recent advances in clinical translation for cancer diagnosis, staging, and therapy.

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Jentzsch, Valerie, Leeza Osipenko, Jack W. Scannell i John A. Hickman. "Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors". JAMA Network Open 6, nr 7 (28.07.2023): e2324977. http://dx.doi.org/10.1001/jamanetworkopen.2023.24977.

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ImportanceThe development of oncology drugs is expensive and beset by a high attrition rate. Analysis of the costs and causes of translational failure may help to reduce attrition and permit the more appropriate use of resources to reduce mortality from cancer.ObjectiveTo analyze the causes of failure and expenses incurred in clinical trials of novel oncology drugs, with the example of insulin-like growth factor-1 receptor (IGF-1R) inhibitors, none of which was approved for use in oncology practice.Design, Setting, and ParticipantsIn this cross-sectional study, inhibitors of the IGF-1R and their clinical trials for use in oncology practice between January 1, 2000, and July 31, 2021, were identified by searching PubMed and ClinicalTrials.gov. A proprietary commercial database was interrogated to provide expenses incurred in these trials. If data were not available, estimates were made of expenses using mean values from the proprietary database. A search revealed studies of the effects of IGF-1R inhibitors in preclinical in vivo assays, permitting calculation of the percentage of tumor growth inhibition. Archival data on the clinical trials of IGF-1R inhibitors and proprietary estimates of their expenses were examined, together with an analysis of preclinical data on IGF-1R inhibitors obtained from the published literature.Main Outcomes and MeasuresExpenses associated with research and development of IGF-1R inhibitors.ResultsSixteen inhibitors of IGF-1R studied in 183 clinical trials were found. None of the trials, in a wide range of tumor types, showed efficacy permitting drug approval. More than 12 000 patients entered trials of IGF-1R inhibitors in oncology indications in 2003 to 2021. These trials incurred aggregate research and development expenses estimated at between $1.6 billion and $2.3 billion. Analysis of the results of preclinical in vivo assays of IGF-1R inhibitors that supported subsequent clinical investigations showed mixed activity and protocols that poorly reflected the treatment of advanced metastatic tumors in humans.Conclusions and RelevanceFailed drug development in oncology incurs substantial expense. At an industry level, an estimated $50 billion to $60 billion is spent annually on failed oncology trials. Improved target validation and more appropriate preclinical models are required to reduce attrition, with more attention to decision-making before launching clinical trials. A more appropriate use of resources may better reduce cancer mortality.

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Moore, Stephen M., James D. Quirk, Andrew W. Lassiter, Richard Laforest, Gregory D. Ayers, Cristian T. Badea, Andriy Y. Fedorov i in. "Co-Clinical Imaging Metadata Information (CIMI) for Cancer Research to Promote Open Science, Standardization, and Reproducibility in Preclinical Imaging". Tomography 9, nr 3 (11.05.2023): 995–1009. http://dx.doi.org/10.3390/tomography9030081.

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Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute’s (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an enabling technology for translational imaging research. Unlike clinical imaging, where equipment manufacturers strive to meet standards in practice at clinical sites, standards are neither fully developed nor implemented in preclinical imaging. This fundamentally limits the collection and reporting of metadata to qualify preclinical imaging studies, thereby hindering open science and impacting the reproducibility of co-clinical imaging research. To begin to address these issues, the NCI co-clinical imaging research program (CIRP) conducted a survey to identify metadata requirements for reproducible quantitative co-clinical imaging. The enclosed consensus-based report summarizes co-clinical imaging metadata information (CIMI) to support quantitative co-clinical imaging research with broad implications for capturing co-clinical data, enabling interoperability and data sharing, as well as potentially leading to updates to the preclinical Digital Imaging and Communications in Medicine (DICOM) standard.

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Nunamaker, Elizabeth A., i Penny S. Reynolds. "‘Invisible actors’—How poor methodology reporting compromises mouse models of oncology: A cross-sectional survey". PLOS ONE 17, nr 10 (20.10.2022): e0274738. http://dx.doi.org/10.1371/journal.pone.0274738.

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The laboratory mouse is a key player in preclinical oncology research. However, emphasis of techniques reporting at the expense of critical animal-related detail compromises research integrity, animal welfare, and, ultimately, the translation potential of mouse-based oncology models. To evaluate current reporting practices, we performed a cross-sectional survey of 400 preclinical oncology studies using mouse solid-tumour models. Articles published in 2020 were selected from 20 journals that specifically endorsed the ARRIVE (Animal Research: Reporting of In Vivo Experiments) preclinical reporting guidelines. We assessed reporting compliance for 22 items in five domains: ethical oversight assurance, animal signalment, husbandry, welfare, and euthanasia. Data were analysed using hierarchical generalised random-intercept models, clustered on journal. Overall, reporting of animal-related items was poor. Median compliance over all categories was 23%. There was little or no association between extent of reporting compliance and journal or journal impact factor. Age, sex, and source were reported most frequently, but verifiable strain information was reported for <10% of studies. Animal husbandry, housing environment, and welfare items were reported by <5% of studies. Fewer than one in four studies reported analgesia use, humane endpoints, or an identifiable method of euthanasia. Of concern was the poor documentation of ethical oversight information. Fewer than one in four provided verifiable approval information, and almost one in ten reported no information, or information that was demonstrably false. Mice are the “invisible actors” in preclinical oncology research. In spite of widespread endorsement of reporting guidelines, adherence to reporting guidelines on the part of authors is poor and journals fail to enforce guideline reporting standards. In particular, the inadequate reporting of key animal-related items severely restricts the utility and translation potential of mouse models, and results in research waste. Both investigators and journals have the ethical responsibility to ensure animals are not wasted in uninformative research.

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Vanhoefer, U., W. Achterrath, H. Wilke i S. Seeber. "Preclinical Evaluation of Irinotecan". Oncology Research and Treatment 23, nr 4 (2000): 2–7. http://dx.doi.org/10.1159/000055047.

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Brown, Timothy, Alireza Mansouri, Samer Zammar i Michael Glantz. "CLRM-11. BENCH TO BEDSIDE NEURO-ONCOLOGY: ADVOCATING FOR A CLINICALLY RELEVANT STRATEGY AS UNDERSCORED BY THE PANDEMIC". Neuro-Oncology Advances 3, Supplement_4 (21.09.2021): iv3. http://dx.doi.org/10.1093/noajnl/vdab112.010.

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Abstract INTRODUCTION The basic science research endeavor has been abundantly and astonishingly successful in the last three decades in elucidating the mechanisms of neuro-oncologic disease and in suggesting therapeutic strategies. Clinical successes have lagged behind, and translation of promising laboratory findings into clinical practice is rare. We hypothesize that one important reason for this discordance is the use of different paradigms for designing laboratory and clinical trials, and that utilizing clinically relevant procedures could improve laboratory study impact. METHODS We identified all pre-clinical neuro-oncology therapeutic trials published in four high-impact journals between 11/2018 and 4/2019 and assigned a level of evidence (LOE) to each study using the American Academy of Neurology evidence classification system. We then identified all phase III trials of therapeutics for COVID and performed the same analysis on all preclinical studies preceding the trials. RESULTS Of the 26 neuro-oncology articles identified, 85% had a LOE of IV and 15% were class III. An analysis of successful human trials showed significantly more high quality laboratory studies supporting “successful” compared to “unsuccessful” trials (p=0.048). This same pattern was identified in phase III trials of COVID. Twenty antiviral studies failed to meet the primary endpoint; all were preceded by class III or IV LOE preclinical studies. Eight evaluable phase three studies of COVID vaccines were identified, all of which met their primary endpoints. These were supported with a mix of Class I/II (n=4) and III/IV (n=4) preclinical studies. Higher LOE by AAN criteria is associated with successful COVID therapeutic trials (p=0.0034). CONCLUSIONS Despite rigorous, elegant, and enlightening laboratory experiments, successful translation to human therapeutics remains rare. Envisioning basic science research through the lens of clinical therapeutics represents a challenging but surmountable paradigm shift that may reverse this pattern and create a more successful research enterprise in neuro-oncology and beyond.

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Begley, C. Glenn. "An Unappreciated Challenge to Oncology Drug Discovery: Pitfalls in Preclinical Research". American Society of Clinical Oncology Educational Book, nr 33 (maj 2013): 466–68. http://dx.doi.org/10.14694/edbook_am.2013.33.466.

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Unfortunately, preclinical research studies frequently suffer from a lack of rigor and robustness that precludes their use as a foundation for a drug-development program. Too often they lack the characteristics that typically are expected in high-quality clinical studies, yet despite that, they are published in top-tier scientific journals. The key attributes that are missing include lack of blinding of investigators, failure to repeat experiments, lack of positive and negative controls, use of nonvalidated reagents, inappropriate use of statistical tests, and data selection (ignoring results that do not fit the hypothesis). Physicians and scientists should view preclinical findings that lack these characteristics with skepticism and should proceed very cautiously in applying such findings to the clinic.

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Ghita, Mihaela, Kathryn H. Brown, Olivia J. Kelada, Edward E. Graves i Karl T. Butterworth. "Integrating Small Animal Irradiators withFunctional Imaging for Advanced Preclinical Radiotherapy Research". Cancers 11, nr 2 (1.02.2019): 170. http://dx.doi.org/10.3390/cancers11020170.

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Translational research aims to provide direct support for advancing novel treatment approaches in oncology towards improving patient outcomes. Preclinical studies have a central role in this process and the ability to accurately model biological and physical aspects of the clinical scenario in radiation oncology is critical to translational success. The use of small animal irradiators with disease relevant mouse models and advanced in vivo imaging approaches offers unique possibilities to interrogate the radiotherapy response of tumors and normal tissues with high potential to translate to improvements in clinical outcomes. The present review highlights the current technology and applications of small animal irradiators, and explores how these can be combined with molecular and functional imaging in advanced preclinical radiotherapy research.

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Dimakakos, Evangelos P., Ioannis Vathiotis i Konstantinos Syrigos. "The Role of Tinzaparin in Oncology". Clinical and Applied Thrombosis/Hemostasis 24, nr 5 (31.10.2017): 697–707. http://dx.doi.org/10.1177/1076029617729215.

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Current guidelines recommend low-molecular-weight heparin treatment in patients with cancer with established venous thromboembolism (VTE). The aim of this article was to study the pharmacological properties and effectiveness of tinzaparin in patients with cancer as well as its potential anticancer properties. A search of PubMed and ScienceDirect databases up to March 2016 was carried out to identify published studies that detect the properties and use of tinzaparin in oncology. Protamine sulfate partially (60% to 65%) neutralized tinzaparin’s anti-Xa activity. No dose adjustment of tinzaparin is needed even in patients with severe renal impairment and Creatinine Clearance ≥20 mL/min. Tinzaparin demonstrated a statistically significant decline in VTE recurrence at 1 year post the index thromboembolic event. A statistically significant reduction in minor bleeding rates was also described, whereas major bleeding events did not decrease in patients with cancer treated with tinzaparin versus those who received vitamin K antagonists. Tinzaparin treatment in patients suffering from deep vein thrombosis reduced the incidence of postthrombotic syndrome and venous ulcers. Tinzaparin’s ability to prevent both metastatic dissemination of cancer cells and tumor angiogenesis has been delineated in preclinical research. Current data show that tinzaparin is safe and efficacious either for short-term or for long-term treatment of VTE in patients with cancer. Clinical trials are needed in order to examine the utility of tinzaparin in primary prevention of VTE and validate its potential anticancer advantages exhibited in preclinical research.

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