Relevant bibliographies by topics / BRAF/RAS wild type

Academic literature on the topic 'BRAF/RAS wild type'

Author: Grafiati
Published: 10 December 2022
Last updated: 29 January 2023

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Journal articles on the topic "BRAF/RAS wild type"

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Landa, Iñigo, Ian Ganly, Timothy A. Chan, Norisato Mitsutake, Michiko Matsuse, Tihana Ibrahimpasic, Ronald A. Ghossein, and James A. Fagin. "Frequent Somatic TERT Promoter Mutations in Thyroid Cancer: Higher Prevalence in Advanced Forms of the Disease." Journal of Clinical Endocrinology & Metabolism 98, no. 9 (September 1, 2013): E1562—E1566. http://dx.doi.org/10.1210/jc.2013-2383.

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Background: TERT encodes the reverse transcriptase component of telomerase, which adds telomere repeats to chromosome ends, thus enabling cell replication. Telomerase activity is required for cell immortalization. Somatic TERT promoter mutations modifying key transcriptional response elements were recently reported in several cancers, such as melanomas and gliomas. Objectives: The objectives of the study were: 1) to determine the prevalence of TERT promoter mutations C228T and C250T in different thyroid cancer histological types and cell lines; and 2) to establish the possible association of TERT mutations with mutations of BRAF, RAS, or RET/PTC. Methods: TERT promoter was PCR-amplified and sequenced in 42 thyroid cancer cell lines and 183 tumors: 80 papillary thyroid cancers (PTCs), 58 poorly differentiated thyroid cancers (PDTCs), 20 anaplastic thyroid cancers (ATCs), and 25 Hurthle cell cancers (HCCs). Results: TERT promoter mutations were found in 98 of 225 (44%) specimens. TERT promoters C228T and C250T were mutually exclusive. Mutations were present in 18 of 80 PTCs (22.5%), in 40 of 78 (51%) advanced thyroid cancers (ATC + PDTC) (P = 3 × 10−4 vs PTC), and in widely invasive HCCs (4 of 17), but not in minimally invasive HCCs (0 of 8). TERT promoter mutations were seen more frequently in advanced cancers with BRAF/RAS mutations compared to those that were BRAF/RAS wild-type (ATC + PDTC, 67.3 vs 24.1%; P < 10−4), whereas BRAF-mutant PTCs were less likely to have TERT promoter mutations than BRAF wild-type tumors (11.8 vs 50.0%; P = .04). Conclusions: TERT promoter mutations are highly prevalent in advanced thyroid cancers, particularly those harboring BRAF or RAS mutations, whereas PTCs with BRAF or RAS mutations are most often TERT promoter wild type. Acquisition of a TERT promoter mutation could extend survival of BRAF- or RAS-driven clones and enable accumulation of additional genetic defects leading to disease progression.
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Calegari, Maria Alessandra, Lisa Salvatore, Brunella Di Stefano, Michele Basso, Armando Orlandi, Alessandra Boccaccino, Fiorella Lombardo, et al. "Clinical, Pathological and Prognostic Features of Rare BRAF Mutations in Metastatic Colorectal Cancer (mCRC): A Bi-Institutional Retrospective Analysis (REBUS Study)." Cancers 13, no. 9 (April 27, 2021): 2098. http://dx.doi.org/10.3390/cancers13092098.

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Recently, retrospective analysis began to shed light on metastatic colorectal cancers (mCRCs) harboring rare BRAF non-V600 mutations, documenting a distinct phenotype and a favorable prognosis. This study aimed to confirm features and prognosis of rare BRAF non-V600 mCRCs compared to BRAF V600E and BRAF wild-type mCRCs treated at two Italian Institutions. Overall, 537 cases were retrospectively evaluated: 221 RAS/BRAF wild-type, 261 RAS mutated, 46 BRAF V600E and 9 BRAF non-V600. Compared to BRAF V600E mCRC, BRAF non-V600 mCRC were more frequently left-sided, had a lower tumor burden and displayed a lower grade and an MMR proficient/MSS status. In addition, non-V600 mCRC patients underwent more frequently to resection of metastases with radical intent. Median overall survival (mOS) was significantly longer in the non-V600 compared to the V600E group. At multivariate analysis, only age < 65 years and ECOG PS 0 were identified as independent predictors of better OS. BRAF V600E mCRCs showed a statistically significant worse mOS when compared to BRAF wild-type mCRCs, whereas no significant difference was observed between BRAF non-V600 and BRAF wild-type mCRCs. Our study corroborates available evidence concerning incidence, clinicopathologic characteristics and prognosis of BRAF-mutated mCRCs.
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Maurel, Joan, Vicente Alonso, Pilar Escudero, Carlos Fernández-Martos, Antonieta Salud, Miguel Méndez, Javier Gallego, et al. "Clinical Impact of Circulating Tumor RAS and BRAF Mutation Dynamics in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy Plus Anti–Epidermal Growth Factor Receptor Therapy." JCO Precision Oncology, no. 3 (December 2019): 1–16. http://dx.doi.org/10.1200/po.18.00289.

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PURPOSE RAS and BRAF mutations can be detected as a mechanism of acquired resistance in circulating tumor (ct) DNA in patients with metastatic colorectal cancer treated with anti–epidermal growth factor receptor therapy. METHODS RAS and BRAF mutational status was assessed in ctDNA in a baseline plasma sample and a serum sample collected at the time of the last available determination (named secondary extraction) from patients with KRAS exon 2 wild-type metastatic colorectal cancer treated in two first-line prospective biomarker-designed clinical trials (PULSE, ClinicalTrials.gov identifier: NCT01288339; and POSIBA, ClincialTrials.gov identifier: NCT01276379). RESULTS Analysis of extended RAS and BRAF in tissue and plasma from 178 patients with KRAS exon 2 wild-type metastatic colorectal cancer showed a sensitivity of 64.1% and a specificity of 90%. The median overall survival (OS) of baseline patients with RAS and BRAF mutations in ctDNA was 22.3 months (95% CI, 15.6 to 29 months) and 8.9 months (95% CI, 6.3 to 11.4 months), respectively, which was significantly inferior to the median OS of 40.4 months (95% CI, 35.9 to 44.9 months) in two patients with wild-type disease ( P < .001). Acquisition of RAS/BRAF mutations occurred in nine of 63 patients (14%) with progressive disease (PD; ie, blood draw within 1 month before PD or after PD) compared with six of 73 patients (8%) with no PD or blood extraction for ctDNA analysis before 1 month of PD ( P = .47). Median OS in patients with RAS/BRAF acquisition was 23.9 months (95% CI, 19.7 to 27.9 months) compared with 40.6 months (95% CI, not reached to not reached) in patients who remained free of mutations ( P = .016). CONCLUSION Our results confirm that baseline RAS and BRAF testing in ctDNA discriminates survival. The emergence of RAS/BRAF mutations has limited relevance for the time to progression to anti–epidermal growth factor receptor therapy.
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Kotoula, Vassiliki, Elias Sozopoulos, Helen Litsiou, Galinos Fanourakis, Triantafyllia Koletsa, Gerassimos Voutsinas, Sophia Tseleni-Balafouta, Constantine S. Mitsiades, Axel Wellmann, and Nicholas Mitsiades. "Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas." Endocrine-Related Cancer 16, no. 2 (June 2009): 565–72. http://dx.doi.org/10.1677/erc-08-0101.

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The serine/threonine kinase B-Raf plays a key role in the Ras/Raf/MEK/ERK pathway that relays extracellular signals for cell proliferation and survival. Several types of human malignancies harbor activating BRAF mutations, most frequently a V600E substitution. The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase (TK) receptor that mediates proliferation and survival signaling, is expressed in a wide variety of normal and neoplastic tissues. EGFR inhibitors have produced objective responses in patients with non-small cell lung carcinomas harboring activating EGFR TK domain somatic mutations. We evaluated the presence of mutations in BRAF (exons 11 and 15), KRAS (exons 1 and 2), NRAS (exons 1 and 2), and EGFR (exons 18–21) in adrenal carcinomas (35 tumor specimens and two cell lines) by DNA sequencing. BRAF mutations were found in two carcinomas (5.7%). Four carcinomas (11.4%) carried EGFR TK domain mutations. One specimen carried a KRAS mutation, and another carried two NRAS mutations. No mutations were found in the two adrenocortical cell lines. BRAF- and EGFR-mutant tumor specimens exhibited stronger immunostaining for the phosphorylated forms of the MEK and ERK kinases than their wild-type counterparts. EGFR-mutant carcinomas exhibited increased phosphorylation of EGFR (Tyr 992) compared with wild-type carcinomas. We conclude that BRAF, RAS, and EGFR mutations occur in a subset of human adrenocortical carcinomas. Inhibitors of the Ras/Raf/MEK/ERK and EGFR pathways represent candidate targeted therapies for future clinical trials in carefully selected patients with adrenocortical carcinomas harboring respective activating mutations.
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Bilgetekin, Irem, Mehmet Dogan, Cengiz Karacin, Fatma Bugdayci Basal, Ece Esin, Gokhan Ucar, Ozlem Aydin Isak, et al. "The temporal evaluation of RAS and BRAF mutation by liquid biopsy at progression after bevacizumab combinations in patients with metastatic colorectal cancer (mCRC)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e15587-e15587. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e15587.

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e15587 Background: Expanded RAS analysis is essential for the selection of biologic agents in mCRC. RAS mutations indicates anti-EGFR unresponsiveness. In this study, we aimed to investigate RAS and BRAF mutations by liquid biopsy at progression in patients with RAS mutant mCRC. Methods: Sixty patients with mCRC who harbored tissue RAS mutations were prospectively analyzed between July 2019 and April 2020. All the patients treated with chemotherapy plus bevacizumab combinations . The plasma samples of the patients were analyzed after progression of bevacizumab combinations. RAS mutation profile was evaluated in plasma using Idylla PCR-based molecular diagnostics method, which enables rapid detection of common mutations in RAS and BRAF genes in circulating tumor DNA (ctDNA). Kaplan-Meier method was used for survival analysis and log-rank test was performed for comparison of groups. Results: The median age of the patients was 60 years (IQR:35-83 years) and female was (n=23, 38.3%). Primary tumor was located in the left colon in 81.7% of all patients. There were 95.0% KRAS and 5% NRAS mutations in baseline tissue biopsy. As a result of liquid biopsy after progression, 55.0% of the patients had KRAS, 3.3% NRAS and 3.3% had BRAF mutations. The RAS mutation detected in 58.3% of the patients. While there was no significant difference in terms of clinicopathological features between wild type (RAS/BRAF) and mutant type (RAS/BRAF) determined by liquid biopsy, the overall survival (OS) of the wild type group was significantly longer than mutant group (43.8 vs. 20.4 months, p= 0.002). Conclusions: This study demonstrated that there may be changes in RAS/BRAF mutation from plasma analysis after progression in patients with mCRC. Since better survival in the patient group with wild type was detected compared to the RAS concordance group, the evaluation of RAS mutation status at the time of progression may be important in terms of disease prognosis and treatment options.
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Wang, Chongkai, Jaideep Sandhu, and Marwan Fakih. "Mucinous Histology Is Associated with Resistance to Anti-EGFR Therapy in Patients with Left-Sided RAS/BRAF Wild-Type Metastatic Colorectal Cancer." Oncologist 27, no. 2 (February 1, 2022): 104–9. http://dx.doi.org/10.1093/oncolo/oyab028.

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Abstract Background Limited studies have suggested that mucinous histology is associated an attenuated response to anti-epidermal growth factor receptor (EGFR) therapy. Methods We conducted a single-institution, retrospective study to review the anti-EGFR response and the molecular profile of patients with left-sided microsatellite stable RAS/BRAF wild-type mucinous metastatic colorectal cancer. Results In comparison to nonmucinous population (n = 98), mucinous histology (n = 20) was associated with a younger age (48 vs 54, P = .02), wild-type APC (80% vs 15.3%, P &lt; .0001), and wild-type TP53 (40% vs 8.2%, P = .001). Guanine nucleotide binding protein, alpha stimulating (GNAS) mutations were exclusively found in mucinous tumors (20% vs 0, P &lt; .0001). Genomic alterations associated with resistance to anti-EGFR therapy, such as ERBB2 amplification, PIK3CA mutation, MAP2K1 mutation, and KRAS amplification, were identified in patients with left-sided RAS/BRAF wild-type mucinous metastatic colorectal cancer. Mucinous histology was not associated with a worse outcome than non-mucinous histology (34.3 vs 42.2 months, P = .85). However, patients with left-sided RAS/BARF wild-type mucinous colorectal cancer treated with first-line anti-EGFR therapy had significantly worse progression-free survival (4 vs 6.5 months, hazard ratio [HR] = 5.3, 95% confidence interval [CI] 1.3-21.7, P = .01) than patients treated with the first-line vascular endothelial growth factor A antibody, bevacizumab. Anti-EGFR therapy was associated with limited responses and a short PFS across all lines of therapy in 12 patients with left-sided RAS/BRAF wild-type mucinous colorectal cancer. Conclusions Mucinous histology is associated with diminished benefits from anti-EGFR therapy in patients with left-sided RAS/BRAF wild-type colorectal cancer. These patients should be considered for bevacizumab-based therapy in the first- and second-line settings.
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Yoshino, Takayuki, Radka Obermannova, Gyorgy Bodoky, Jana Prausová, Rocio Garcia-Carbonero, Tudor-Eliade Ciuleanu, Pilar Garcia Alfonso, et al. "Are BRAF mutated metastatic colorectal cancer (mCRC) tumors more responsive to VEGFR-2 blockage? Analysis of patient outcomes by RAS/RAF mutation status in the RAISE study—A global, randomized, double-blind, phase III study." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 622. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.622.

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622 Background: The RAISE trial (NCT01183780) demonstrated that ramucirumab (RAM) plus leucovorin, fluorouracil, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo (PBO) plus FOLFIRI as second-line mCRC treatment. RAS/RAF mutations are associated with resistance to anti-EGFR therapies and poor prognosis, particularly BRAF mutations. The extensive RAISE biomarker program assessed the association of multiple candidate markers with efficacy outcomes. Here we present the results for RAS/ RAF mutations. Methods: Plasma and tumor tissue collection were mandatory. KRAS mutation status was determined locally before randomization. Further RAS and RAF mutations were assessed centrally by multiplex qPCR using the Modaplex system (Qiagen) only in samples that were initially reported as KRAS wild type. Thus, patients were classified into one of the 3 categories in the table. OS and PFS by RAS and RAF subgroups were evaluated by Kaplan-Meier and Cox proportional hazards analyses. Results: As with previously reported KRAS analyses, the favorable RAM treatment effect was similar between patients with expanded RAS mutations compared with patients with RAS/ RAF wild-type tumors. However, in the 41 patients with BRAF mutated tumors, the RAM benefit was even more notable for both OS (hazard ratio [HR] 0.54; 95% CI 0.25–1.13) and PFS (HR 0.55; 95% CI 0.28–1.08). Conclusions: RAISE demonstrated that the addition of RAM to FOLFIRI improved patient outcomes regardless of RAS mutation status. The noteworthy signal for patients with BRAF mutant tumors is encouraging due to their poor prognosis but requires further validation in other clinical trials. Clinical trial information: NCT01183780. [Table: see text]
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Conroy, Jeffrey M., Sarabjot Pabla, Marc S. Ernstoff, Igor Puzanov, Mary Nesline, Sean T. Glenn, Antonios Papanicolau-Sengos, et al. "Comprehensive immune and mutational profile of melanoma." Journal of Clinical Oncology 36, no. 5_suppl (February 10, 2018): 182. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.182.

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182 Background: The association between tumor mutational profiles and immune signatures has not been well-characterized. Methods: 306 melanoma samples were tested by NGS using a comprehensive cancer panel for mutational status and an immune response panel which interrogates the expression profile of 54 validated immune-related genes. The ranking of gene expression, mutational burden and 7 immune phenotypes was compared to a reference population. 38% cases were positive for activating BRAF mutations, 12% for RAS, and 6% for NF1. The remaining 44% were considered triple wild type. Principal component analysis (PCA) followed by hierarchical clustering was performed to determine association of BRAF/RAS/NF1 mutations and triple wild type with immune phenotypes, mutational burden and gene expression as measured by the NGS panels. Results: PCA showed that the first and second dimension explain 86% of the variation in the mutation profiles of the 306 melanomas. The first principal component highly correlated with BRAF positive status (pval < 0.001), the second highly correlated with RAS positive status (pval < 0.001), and the third principal component, although not informative, highly correlated with NF1 status (pval < 0.001) and Mutation Burden (pval < 0.001). Hierarchical clustering of the samples resulted in 4 distinct clusters: RAS positive, BRAF Positive, NF1 positive and triple wild type. The RAS positive cluster demonstrated significantly lower expression of ICOSLG, ICOS, CD4, C10orf54, CD40 and CD244 genes. Similarly, the BRAF positive cluster under-expresses immune escape and proinflammatory immune phenotypes, but over-expressed OX40L. The NF1 positive cluster had significantly higher mutational burden than other clusters. On the contrary, the triple wild type cluster over-expressed 6 out of 7 immune phenotypes. Conclusions: BRAF/RAS/NF1 mutation status are immunophenotypically distinct and do not associate with a typical immune phenotype in the tumor microenvironment. Triple wild type samples present with an overall activated immune phenotype, representative of an inflamed tumor. Additional studies are necessary to include additional activating or loss of function mutations to expand these findings.
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Romano, David, Lucía García-Gutiérrez, Nourhan Aboud, David J. Duffy, Keith T. Flaherty, Dennie T. Frederick, Walter Kolch, and David Matallanas. "Proteasomal down-regulation of the proapoptotic MST2 pathway contributes to BRAF inhibitor resistance in melanoma." Life Science Alliance 5, no. 10 (August 29, 2022): e202201445. http://dx.doi.org/10.26508/lsa.202201445.

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The RAS-RAF-MEK-ERK pathway is hyperactivated in most malignant melanomas, and mutations in BRAF or NRAS account for most of these cases. BRAF inhibitors (BRAFi) are highly efficient for treating patients with BRAFV600E mutations, but tumours frequently acquire resistance within a few months. Multiple resistance mechanisms have been identified, due to mutations or network adaptations that revive ERK signalling. We have previously shown that RAF proteins inhibit the MST2 proapoptotic pathway in a kinase-independent fashion. Here, we have investigated the role of the MST2 pathway in mediating resistance to BRAFi. We show that the BRAFV600E mutant protein, but not the wild-type BRAF protein, binds to MST2 inhibiting its proapoptotic signalling. Down-regulation of MST2 reduces BRAFi-induced apoptosis. In BRAFi-resistant cell lines, MST2 pathway proteins are down-regulated by ubiquitination and subsequent proteasomal degradation rendering cells refractory to MST2 pathway–induced apoptosis. Restoration of apoptosis can be achieved by increasing MST2 pathway protein expression using proteasome inhibitors. In summary, we show that the MST2 pathway plays a role in the acquisition of BRAFi resistance in melanoma.
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Dillon, Martha, Antonio Lopez, Edward Lin, Dominic Sales, Ron Perets, and Pooja Jain. "Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers." Cancers 13, no. 20 (October 10, 2021): 5059. http://dx.doi.org/10.3390/cancers13205059.

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The mitogen-activated protein kinase (MAPK) pathway, consisting of the Ras-Raf-MEK-ERK signaling cascade, regulates genes that control cellular development, differentiation, proliferation, and apoptosis. Within the cascade, multiple isoforms of Ras and Raf each display differences in functionality, efficiency, and, critically, oncogenic potential. According to the NCI, over 30% of all human cancers are driven by Ras genes. This dysfunctional signaling is implicated in a wide variety of leukemias and solid tumors, both with and without viral etiology. Due to the strong evidence of Ras-Raf involvement in tumorigenesis, many have attempted to target the cascade to treat these malignancies. Decades of unsuccessful experimentation had deemed Ras undruggable, but recently, the approval of Sotorasib as the first ever KRas inhibitor represents a monumental breakthrough. This advancement is not without novel challenges. As a G12C mutant-specific drug, it also represents the issue of drug target specificity within Ras pathway; not only do many drugs only affect single mutational profiles, with few pan-inhibitor exceptions, tumor genetic heterogeneity may give rise to drug-resistant profiles. Furthermore, significant challenges in targeting downstream Raf, especially the BRaf isoform, lie in the paradoxical activation of wild-type BRaf by BRaf mutant inhibitors. This literature review will delineate the mechanisms of Ras signaling in the MAPK pathway and its possible oncogenic mutations, illustrate how specific mutations affect the pathogenesis of specific cancers, and compare available and in-development treatments targeting the Ras pathway.
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Dissertations / Theses on the topic "BRAF/RAS wild type"

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Rebecca, Vito William. "Potential Targeted Therapeutic Strategies for Overcoming Resistance in BRAF Wild Type Melanoma." Scholar Commons, 2014. http://scholarcommons.usf.edu/etd/5112.

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Melanoma manifests itself from the malignant transformation of melanocytes and represents the deadliest form of skin cancer, being responsible for the disproportionate majority of all skin cancer deaths. The 2002 discovery that 50% of all melanoma patients possess activating BRAF mutations ignited a significant paradigm shift in the way the melanoma field approached research and how patients were treated [1]. The era of targeted therapy had begun and with it came successful targeted BRAF inhibitor therapy regimens, which have accomplished improved clinical benefit (response rate, progression free survival, and overall survival) compared with treatment with chemotherapy in three phase III clinical trials [2]. Although there has been much success in the subgroup of patients whose melanomas harbor activating BRAF mutations, approximately 50% of all melanoma patients do not harbor BRAF mutations. This subgroup of melanoma is composed of ~15-20% of all patients with NRAS mutations and another ~25-30% of patients with neither BRAF nor NRAS mutations. Successful targeted treatment strategies are currently lacking for this subgroup of BRAF-wild type melanomas and therefore novel targeted therapeutic modalities are urgently needed. The work described in this dissertation sheds light on potential approaches for the treatment of BRAF wild type melanoma and will be split into three separate strategies. The first will focus upon the treatment of melanomas without BRAF or NRAS mutations (BRAF/NRAS wild type melanoma) and will expand upon a clinical observation where two melanoma patients were treated with an experimental combination of carboplatin and paclitaxel, with the addition of the AKT inhibitor MK-2206. We demonstrate that the inhibition of AKT significantly enhances the efficacy of chemotherapy in a reactive oxygen species (ROS) mediated fashion, and an induction of autophagy plays a cyto-protective role. The second story focuses upon the treatment of NRAS mutant melanomas by investigating resistance mechanisms to MEK inhibitor treatment. We discovered a MEKi-mediated induction of receptor tyrosine kinase (RTK) signaling to serve as a significant mechanism of escape for NRAS mutant melanomas treated chronically with the MEK inhibitor AZD6244, as well as the recently U.S. Food and Drug Administration (FDA) approved MEK inhibitor trametinib. Novel targeted therapy combinations were then added to overcome the escape from MEK inhibitor therapy. Co-targeting of the receptor tyrosine kinases AXL, PDGFR-β and c-MET with a pan-RTK inhibitor, as well as the mitogen-activated protein kinase (MAPK) pathway with a MEK inhibitor greatly enhanced treatment-induced apoptosis and inhibition of proliferation. The final strategy builds upon the observation that single agent MEK-inhibition is largely ineffective in the treatment of NRAS mutant melanomas. A recovery of MAPK pathway activity in response to MEK inhibition was established to play a significant role in escape of NRAS mutant cells from cell cycle arrest and apoptosis. The combination of a MEK inhibitor with the novel ERK inhibitor VTX-11e prevents the onset of resistant clones and enhances cytotoxicity of the NRAS mutant melanoma cells. This body of work establishes original targeted therapy combinations for the treatment of both NRAS mutant melanomas and BRAF/NRAS wild type melanomas. We propose future clinical investigation with these strategies in the treatment of BRAF wild type melanoma patients in hopes to further extend overall survival.
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Moka, Nagaishwarya, Kelley cross, Marianne Brannon, Janet Lightner, Megan Dycus, William Stone, Victoria Palau, and Koyamangalath Krishnan. "Delta-tocotrienol and simvastatin induces differential cytotoxicity and synergy in BRAF wild-type SK-MEL-2 and mutant BRAF SK-MEL-28 melanoma cancer cells." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/215.

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Targeting the mutant BRAF and immunotherapy are new approaches to the treatment of metastatic malignant melanoma that has significantly improved survival but is associated with significant toxicity and cost. Potent and specific BRAF inhibitors like vemurafenib and dabrafenib are superior to chemotherapy in treatment of BRAF mutant melanomas which represent nearly 50% of all melanomas. A less toxic approach to treatment of malignant melanoma is hence appealing. Delta-tocotrienol (DT3), an unsaturated vitamin E isoform, and simvastatin, an HMG-CoA reductase inhibitor have been shown to have anti-neoplastic properties. We studied the effects of these chemicals in both BRAF-mutated SK-MEL-28 and BRAF-wild type SK-MEL-2 melanoma cells. MTS assays were used to analyze cytotoxicity. SK-MEL-28 and SK-MEL-2 cells were cultured in MEM media containing 10% serum and plated in 96-well culture plates for 48 hours then treated with DT3 (0-80 µM), simvastatin (0-10 µM), or a combination and dosed again at 72 hours. SK-MEL-28 and SK-MEL-2 cells were grown in 60 mm plates and treated with DT3 at concentrations of 30 µM, simvastatin at concentrations of 10 µM and combination of DT3 and simvastatin at concentrations of 10 µM and 2 µM. Cell were lysed with RIPPA buffer with protease and phosphatase inhibitor after 6 hours of treatment. Protein concentration of cell lysates was measured spectrophotometrically (GLO Max Multi+, Promega), using a BCA protein assay kit. The samples were run in SDS PAGE and blotted onto nitrocellulose membranes. Membranes were incubated with antibodies against Hsp 70 (Enzo Life Sciences, Farmingdale, NY), Hsp 90 (Santa Cruz, Dallas, TX), pS6 and pERK (Cell Signaling, Danvers, MA) and pAKT. Using MTS assay, we found that DT3 (IC50 75.2 μM) and simvastatin (IC50 8.3μM) have cytotoxic effects on melanoma cell line SK-MEL-2, but not on the SK-MEL-28 cells DT3 and simvastatin at the concentrations studied (10-80 μM DT3) and (0.625- 10 μM simvastatin). Further studies determined that simvastatin decreased expression of pS6, pERK on SK-MEL-2 and not DT3. However, these effects are different in SK-MEL-28 cells where there is only decrease in expression of pS6; treated SK-MEL-2 cells also show over-expression of Hsp70 suggestive of a rescue effect leading to lesser cytotoxic activity. The selective cytotoxicity observed in wild type BRAF melanoma cell lines by DT3 and simvastatin warrants further research into the potential therapeutic use of these drugs. A differential cytotoxicity is shown by DT3 and simvastatin in malignant melanoma cells with selective more potency in wild type BRAF melanoma compared to mutant BRAF melanoma cells. Further studies will be undertaken to dissect the mechanistic basis of this differential response.
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Ferguson, Robert. "Wild-type N-Ras complements mutant K-Ras in pancreatic cancer cell lines but K-Ras has a specific role in cell cycle independent regulation of G2 cyclins." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2032380/.

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Pancreatic Ductal Adenocarcinoma (PDAC) is nearly always associated with mutant K-Ras. Nevertheless, targeting oncogenic K-Ras has so far proved ineffective in treating this form of cancer and pancreatic cancer cell lines can become K-Ras independent. Other forms of Ras are rarely mutated but wild type N-Ras and H-Ras have been shown to be present alongside functional K-Ras mutations and have been demonstrated to increase responsiveness to growth factors. Beyond this little evidence had previously been gathered on the activity or function of N-Ras and H-Ras in PDAC. Therefore, this thesis aimed to determine if other Ras isoforms are active in PDAC cell lines and what effect they may have on controlling cell division, oxidative metabolism, cytokine expression and the phospholipid composition of the membrane. The presence of active N-Ras and K-Ras was identified in three of the four human PDAC cell lines tested. Only active K-Ras was detected in a cell line derived from a mouse model of pancreatic cancer driven by heterologous expression of mutant KRAS. N-Ras was shown to be functioning alongside K-Ras to control the relative level of oxidative metabolism in the Suit-2 and a faster growing variant of the Panc-1 cell lines, but K-Ras acts alone in the slow growing Panc-1 cell line that does not contain N-Ras. N-Ras and K-Ras were shown to have different effects on the levels of cytokines, although K-Ras is largely independent of N-Ras in its regulation of phospholipid composition. A novel N-Ras independent mechanism for K-Ras transcriptional control of cyclin B1 was demonstrated. When K-Ras is depleted cyclin B1 and cyclin A are decreased. Cyclin B1 transcription can be rescued by inhibition of the Proteasome. A model is proposed whereby an unknown protein or proteins activates cyclin B1 transcription in a cell-cycle independent fashion and is protected from proteasomal degradation by K-Ras. These results suggest that mutant K-Ras can act in conjunction with wild-type N-Ras, but also can function independently to regulate G2 cyclins.
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Sree, Kumar Shalini. "Biomarkers of resistance to anti-EGFR in wild type KRAS/BRAF colorectal cancer cell lines." Thesis, 2015. http://hdl.handle.net/2440/104679.

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Colorectal cancer (CRC) is a leading cause of cancer death worldwide and despite significant improvement the median survival remains relatively poor. The use of targeted therapies like cetuximab and panitumumab inhibiting the epidermal growth factor receptor (EGFR) offer promise in improving patient outcomes. However, a high proportion of CRC patients show resistance to anti-EGFR therapy. Biomarkers such as mutant KRAS or BRAF predict resistance to anti-EGFR therapy in only a subset of patients and we hypothesise that other biomarkers for resistance to EGFR targeted therapies exist. The studies presented in this thesis aimed to determine other biomarkers of resistance to anti-EGFR therapy in wild type KRAS and BRAF CRC cell lines. Following RT-Profiler Array analysis, the 3 most significantly upregulated genes amongst the 3 anti-EGFR resistant CRC cell lines (SNU-C1, SW48 and COLO-320DM) were chosen as candidate biomarkers of resistance: HBEGF (heparin-binding epidermal growth factor-like growth factor), EGR1 (early growth response protein 1) and AKT3 (protein kinase B gamma) were validated using qRT-PCR. HBEGF is a member of EGF-like growth factor family is a potent inducer of tumour growth, angiogenesis, and implicated in metastasis. EGR1 is a transcription factor implicated in cell growth, survival, transformation, tumour progression. AKT3 is a serine/threonine kinase and a downstream mediator of PI3K-AKT-mTOR pathway resulting in cell proliferation, cell survival and angiogenesis. HBEGF was knocked down by 79.4% in SNUC1, EGR1 was knocked down by 85.6% in SW48 and AKT3 was knocked down by 95.3% in COLO-320DM, as validated by qRT-PCR and western blot. Following knockdown, these cell lines were treated with anti-EGFR, and SNU-C1 had proliferation rate of 49.1% (83.8% before knockdown), SW48 yielded proliferation rate of 46.9% (70% before knockdown) and COLO-320DM had proliferation rate of 64.1% (68.3% before knockdown). This suggests that the resistant phenotype of these cell lines was reversed. The expression of these markers was also elucidated using immunohistochemistry on mCRC primary tumour tissues from 10 patients that had undergone cetuximab monotherapy. Some 50% of these patients had overexpression of two or more of these markers, and these patients did not respond to cetuximab, suggesting that these overexpressed biomarkers might be involved in circumventing cetuximab to confer resistance. One of the studies presented in this thesis also explored the KRAS G13D phenomenon and the effect of cetuximab and panitumumab on cell lines harbouring different mutational status. Previous clinical studies have demonstrated that a proportion of KRAS G13D harbouring tumour patients respond to the anti-EGFR therapies, and a large proportion of KRAS WT patients do not respond. After treatment with cetuximab or panitumumab, the KRAS G13D mutant cell lines showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line and the sensitive WT KRAS cell line. One of the G13D cell lines was significantly more sensitive to panitumumab than to cetuximab. This study demonstrated that specific KRAS mutation determines the responsiveness to anti-EGFR monoclonal antibody treatment, corresponding to previously reported clinical observations. In conclusion, the studies presented in this thesis have demonstrated that components of EGFR signalling cascade have emerged as important biomarkers of resistance for anti-EGFR targeted therapies. Further assessment of the molecular mechanisms that dictate this resistance and identification of other specific biomarkers for these agents will provide valuable information to identify the most effective therapy for primary and mCRC patients.
Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medical Sciences, 2015.
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Weyandt, Jamie Dawn. "Investigatiing the Role of the Wild-Type Ras Isoforms in KRas-driven Cancer." Diss., 2015. http://hdl.handle.net/10161/11392.

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The RAS family is a group of small GTPases that can become constitutively activated by point mutations that are found in about 30% of all cancer patients. There are three well-characterized RAS family members: HRAS, NRAS, and KRAS, the latter of which is alternatively spliced at the C-terminus into KRAS4A and KRAS4B. The RAS proteins are all nearly identical at their N-termini and core effector binding domains, but have divergent C-terminal membrane-binding regions that impart different subcellular localization and subtle differences in signaling. Although the role of constitutively activated oncogenic RAS has been well established to play a role in cancer, recent work has suggested that wild-type RAS signaling may also be important in tumorigenesis. Wild-type RAS proteins have been shown to be activated in the presence of oncogenic KRAS. However, the consequences of this activation are context-dependent, as signaling through the wild-type RAS proteins has been shown to both suppress neoplastic growth and promote tumorigenesis under different circumstances.

I sought to investigate the role of the wild-type RAS proteins in two clinically –relevant models of cancer: pancreatic, the type of cancer most frequently associated with KRAS mutations, and lung cancer, the cancer in which KRAS mutations affect the highest number of patients. First, I tested whether a loss of wild type Hras altered tumorigenesis in a mouse model of pancreatic cancer driven by oncogenic Kras. Hras homozygous null mice (Hras-/- ) exhibited more precancerous lesions of the pancreas as well as more off-target skin papillomas compared to their wild type counterparts, indicating that Hras suppresses early Kras-driven pancreatic tumorigenesis. Loss of Hras also reduced the survival of mice engineered to develop aggressive pancreatic cancer by the additional disruption of one allele of the tumor suppressor p53 (Trp53R172H/+). However, this survival advantage was lost when both alleles of Trp53 were mutated, suggesting that wild-type HRas inhibits tumorigenesis in a p53-dependant manner.

Next, I investigated the role that wild-type Hras and Nras play in a chemical carcinogen-induced model of lung cancer. In mice treated with urethane, a carcinogen that induces Kras-mutation positive lung lesions, Hras-/ mice once again developed more tumors than wild-type mice. Interestingly, however, this effect was not observed in mice lacking wild-type Nras. Mice lacking both Hras and Nras alleles developed approximately the same number of tumors as Hras-/- mice, thus the additional loss of Nras does not appear to enhance the tumor-promoting effects of loss of Hras. In summary, signaling through wild-type Hras, but not Nras, suppresses tumorigenesis in a carcinogen-induced model of lung cancer.

The tumor-suppressive effects of wild-type Ras signaling were traced to the earliest stages of pancreatic tumorigenesis, suggesting that wild-type Ras signaling may suppress tumorigenesis as early as the time of initiation. These findings suggest that differences in expression of the wild-type Ras isoforms could potentially play a role in an individual’s predisposition for developing cancer upon oncogenic insult.


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Chun-ILi and 李俊毅. "The effect of miR-146a and target gene vimentin on tumorigenesis of esophageal squamous cell carcinoma cell lines overexpressing wild-type K-Ras gene." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/b64k4e.

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Book chapters on the topic "BRAF/RAS wild type"

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Chandra, Sunandana, Grant McArthur, and Jeffrey Sosman. "Molecularly Targeted Therapy for Patients with BRAF Wild-Type Melanoma." In Cutaneous Melanoma, 1–22. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-319-46029-1_55-1.

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Chandra, Sunandana, Grant A. McArthur, and Jeffrey Sosman. "Molecularly Targeted Therapy for Patients with BRAF Wild-Type Melanoma." In Cutaneous Melanoma, 1087–108. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-05070-2_55.

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Wittinghofer, Alfred, Sybille M. Franken, Axel J. Scheidig, Hans Rensland, Alfred Lautwein, Emil F. Pai, and Roger S. Goody. "Three-Dimensional Structure and Properties of Wild-Type and Mutant H-ras-Encoded p21." In Ciba Foundation Symposium 176 - The GTPase Superfamily, 6–27. Chichester, UK: John Wiley & Sons, Ltd., 2007. http://dx.doi.org/10.1002/9780470514450.ch2.

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Kataoka, Keiko. "Fermented Brown Rice as a Functional Food." In Rice [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98840.

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Brown rice, especially in a part of rice bran, contains many kinds of nutrients and biologically active components such as plant polyphenols and phytic acid, but is hard to eat. “Brown rice and rice bran fermented with Aspergillus oryzae (FBRA)” is a processed food that is easier for daily intake, commercially available, and rich in eating experience. During the fermentation process, dietary fibers is partially digested, and free vitamins and phenolic compounds have increased. These fermentation products are utilized for quality control to manage FBRA production. Recently, plant-derived polyphenols have shown anti-oxidative activity and biological function in various disease models. We and other research groups used raw powder FBRA to examine its biological activity through pathological and/or molecular biological analysis. Dietary administration of FBRA showed anti-tumorigenic effects in chemically induced tumors in rodents. Anti-inflammatory effects have been observed in DSS-induced colitis in rat and inflammation-mediated rodent tumor models. I will give an outline of the characteristic of FBRA, and then introduce our recently published work about “Preventive effect of FBRA on spontaneous type 1 diabetes in NOD female mice”, including how to estimate the in vivo effect of dietary FBRA, its possible mechanisms and the limit of this study.
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Babu, Geethu, R. Rejnish Ravi Kumar, Malu Rafi, Lekha M. Nair, Zuzaki Sharafuddin, John Mathew, Nijo Jose, and Cessal Thommachan Kainickal. "Systemic Therapy in Thyroid Cancer." In Thyroid Cancer - The Road From Genes to Successful Treatment [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.106462.

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The standard treatment for patients with differentiated thyroid cancer (DTC) is a combination of surgery, radioactive iodine (RAI), and long-term thyroid hormone–suppression therapy. Treatment of patients whose diseases persist, recur, or metastasize remains a challenge. The role of cytotoxic chemotherapy in the treatment of thyroid cancer is limited. The key signaling pathways involved in the pathogenesis of thyroid cancers are the RAS/RAF/MEK & PI3K/Akt/mTOR pathways. Systemic therapy in thyroid cancer involves the use of tyrosine kinase inhibitors targeting the above mentioned pathways which are often both effective in controlling disease and have manageable toxicity. Sorafenib and lenvatinib are approved for advanced radioiodine refractory and poorly differentiated thyroid cancers and vandetanib and cabozantinib for recurrent or metastatic medullary thyroid cancers. Cabozantinib is also approved for the treatment of locally advanced or metastatic radioactive iodine–refractory differentiated thyroid cancer that has progressed after prior VEGF-targeted therapy. The combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) is approved for BRAF V600E mutated unresectable locally advanced anaplastic thyroid cancer. Selpercatinib, RET kinase inhibitor is used for advanced and metastatic RET mutated medullary thyroid cancers and advanced and metastatic RET fusion-positive thyroid cancers of any histologic type. Various clinical trials using newer molecules targeting the aforementioned pathways are ongoing.
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Jinga, Dan-Corneliu, and Maria-Ruxandra Jinga. "Immunotherapy of Metastatic Melanoma." In Melanoma - Standard of Care, Challenges, and Updates in Clinical Research [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.105585.

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Immunotherapy is part of the new treatments that significantly improved the prognostic of metastatic melanoma patients. The article reviews briefly the old immunotherapeutic approaches e.g., interferon-ᾳ2 and interleukin-2, and focuses on immune checkpoint inhibitors such as anti-CTLA-4 inhibitors and anti-PD-1 inhibitors in monotherapy or in combination (dual immune blockade). We detailed the results from CheckMate and KEYNOTTE clinical trials that lead to US Food and Drug Administration and European Medicines Agency approvals of the new agents for the treatment of advanced melanoma. The chapter concentrates on the algorithms for BRAF wild-type and BRAF mutated metastatic melanoma treatments, according to American (NCCN) and European (ESMO) guidelines. We underlined the first line, second line, and subsequent lines of treatment for both melanoma subtypes and for particular cases, such as in-transit metastasis or brain metastasis. A special attention was paid to treatment options for early and late disease progression (primary and acquired resistance after adjuvant therapy). Unfortunately, the new immune agents produce a higher toxicity rate, mainly immune adverse events. Also, these drugs can interact with the gut microbiome and with antibiotics, decreasing the efficacy of immune therapy. Finally, we review the new directions for immune therapy e.g., new immune combinations, the association of immune and targeted therapies, and adoptive cellular therapy with tumor-infiltrating lymphocytes, interleukin-2, and anti-PD-1.
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Tizro, Parastou, Rami Abdulbaki, Anita Aggarwal, Aaron Auerbach, and Victor E. Nava. "Splenic B-Cell Lymphoma/Leukemia, Unclassifiable." In Lymphoma [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.101418.

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Splenic B-cell lymphoma/leukemia, which is unclassifiable, includes low-grade B-cell lymphoproliferative disorders that do not fit into any other splenic lymphoid neoplasm based on current WHO classification. Presently, two provisional entities, splenic diffuse red pulp small B-cell lymphoma (SDRPL) and hairy-cell leukemia variant (HCL-v), are the most recognizable members of this group. SDRPL is an uncommon malignancy representing less than 1% of all non-Hodgkin lymphomas. Frequent clinical manifestations include splenomegaly and lymphocytosis. SDRPL is currently considered a diagnosis of exclusion and requires clinical and paraclinical correlation, including blood smear, bone marrow and spleen morphology, and the correct immunophenotype (typically positive for CD20, DBA.44, and IgG; and negative for CD5, CD10, CD23, CD43, annexin A1, CD11c, CD25, CD103, and CD123), and cytogenetic findings. Cyclin D3 is expressed in the majority of SDRPL in contrast to other types of small B-cell lymphomas. HCL-v is a less common disease accounting for 0.4% of all chronic lymphoproliferative disorders. It resembles classical HCL and SDRPL by diffusely infiltrating the splenic red pulp but is considered biologically unrelated. Splenomegaly and atypical lymphocytosis without monocytopenia are common. Distinguishing features of HCL-v include morphology, immunophenotype (the absence of CD25, CD200, CD123, annexin A1, and TRAP), genotype (wild-type BRAF), and prognosis.
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Conference papers on the topic "BRAF/RAS wild type"

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Poulikakos, Poulikos I., Chao Zhang, Eric W. Joseph, Yogindra Persaud, Christine A. Pratilas, Gideon Bollag, David B. Solit, Kevan M. Shokat, and Neal Rosen. "Abstract LB-190: RAF inhibitors transactivate RAF dimers and ERK signaling in a wild-type BRAF-dependent manner." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-lb-190.

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Capparelli, Claudia, Nadège Gaborit, Yosef Yarden, and Andrew Aplin. "Abstract C44: Targeting neuregulin1-ErbB3 signaling in wild-type BRAF/NRAS melanoma." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-c44.

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Popovici, Vlad, Eva Budinska, Sabine Tejpar, Arnaud Roth, Fredrik Bosman, Scott Weinrich, Graeme Hodgson, and Mauro Delorenzi. "Abstract 4722: A BRAF-mutated gene expression signature identifies BRAF wild type colon cancer patients with poor prognosis." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-4722.

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Ming, Zizhen, Su Yin Lim, Richard F. Kefford, and Helen Rizos. "Abstract 765: Multiple signalling pathways are active in BRAF/NRAS wild type melanomas." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-765.

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Zhang, Yanping, Guangyong Peng, and Eddy C. Hsueh. "Abstract 375: Combination of MEK and PI3K inhibition in BRAF wild-type and mutant melanoma." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-375.

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Banjin, Maja, Amina Jalovčić, and Velda Smajlbegović. "CILJANA TERAPIJA I METASTATSKI MELANOM." In Okrugli sto s međunarodnim učešćem "Melanom". Akademija nauka i umjetnosti Bosne i Hercegovine, 2018. http://dx.doi.org/10.5644/pi2019.180.02.

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Melanom je globalni zdravstveni problem s kontinuiranim porastom u incidence. Rezultati tretmana metastatskog melanoma su, do skorašnjih napredovanja u terapijama, bili slabi, s medijanom ukupnog preživljavanja (OS) od 7,5 mjeseci i petogodišnjom stopom preživljavanja 6%. U kliničkim istraživanjima za metastatski melanom, selektivni inhibitori BRAF gena, vemurafenib i dabrafenib, pokazali su značajnu antitumorsku aktivnost i poboljšanje u OS i PFS kada se porede s dakarbazinom. Međutim, skoro će svaki pacijent tretiran BRAF inhibitorima imati progresiju bolesti, a tumori pokazuju reaktivacije MAPK puta u vrijeme pojave rezistencije. Specifična BRAF inhibicija vodi ka paradoksalnoj aktivaciji ćelija s RAS divljim “wild” genom uzvodno u MAPK putu i iz tih razloga vodi rezistenciji na terapiju, ćelijskoj proliferaciji i povećanoj stopi RAS kožnog toksiciteta. Pretklinički podaci sugerisali su da inhibitori MEK gena u MAPK putu mogu da zaustave rast i isprovociraju ćelijsku smrt kod nekih BRAF pozitivnih melanomskih tumora. Selektivni inhibitori MEK1 i MEK2 su cobimetinib i trametinib. Kombinovanjem BRAF+MEK inhibicije postiže se produženje terapijskog odgovora, odgađanje rezistencija i smanjuje pojava novih kutanih SCC/KA udruženih s BRAF inhibicijom. Kombinacija dabrafenib+ trametinib i vemurafenib+cobimetinib odobrena je za pacijente s neresktabilnim ili metastatskim melanomom s tumorima koji imaju mutaciju na BRAF genu. Klinička vrijednost intermitentne terapije za sada nije definisana. Podaci iz kliničkih istraživanja sugerišu da selekcionirani pacijenti mogu imati benefit od terapije uprkos razvijanju novih metastaza. Uvođenje ovih terapija u adjuvantno područje može dodatno poboljšati ishod i liječenje ove bolesti.
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Rosenbaum, Sheera, Claudia Capparelli, Lisa D. Berman-Booty, Nadège Gaborit, Tingting Zhan, Michael A. Davies, Yulius Y. Setiady, Yosef Yarden, and Andrew E. Aplin. "Abstract A52: Extracellular matrix regulation of ErbB3 in a subset of wild-type BRAF/NRAS melanoma." In Abstracts: AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; September 14-17, 2014; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-8514.pi3k14-a52.

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Fragomeni, Roberto A. Salas, Hye-Won Chung, Sharon Shacham, Michael Kauffman, and James C. Cusack. "Abstract 1914: Potent anticancer activity against both BRAF-mutant and BRAF wild-type melanoma cell lines using a novel CRM1 nuclear export inhibitor." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-1914.

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Haendler, Bernard, Kathy A. Gelato, Laura Schöckel, Tatsuo Sugawara, Pascale Lejeune, Heidrun Ellinger-Ziegelbauer, Amaury E. Fernandez-Montalvan, et al. "Abstract 4703: The BET inhibitor BAY 1238097 shows efficacy in BRAF wild-type and mutant melanoma models." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-4703.

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Essner, Richard, Ke Wei Gong, David Kaufman, Hsiaowang Chen, Charles Ginther, Judy Dering, Erika von Euw, Bartosz Chmielowski, Richard Finn, and Dennis Slamon. "Abstract A26: Protein phosphatase 4 (PP4) as a potential therapeutic target gene for BRAF wild type melanoma." In Abstracts: AACR Special Conference on Advances in Melanoma: From Biology to Therapy; September 20-23, 2014; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.mel2014-a26.

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