BRAF Inhibitor Therapy for Melanoma, Thyroid and Colorectal Cancers: Development of Resistance and Future Prospects

Rahman, Atiqur; Salajegheh, Ali; Smith, Robert A.; Lam, Alfred King‐Yin

doi:10.2174/1568009614666140121150930

Cited by 34 publications

(28 citation statements)

References 151 publications

(241 reference statements)

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“…BRAF is highly mutated in various cancers including melanoma, thyroid and colorectal cancers [30]. The most common V600E mutation renders BRAF V600E constitutively active.…”

Section: Introductionmentioning

confidence: 99%

Two is better than one; toward a rational design of combinatorial therapy

Chen

Lahav

2016

Current Opinion in Structural Biology

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Drug combination is an appealing strategy for combating the heterogeneity of tumors and evolution of drug resistance. However, the rationale underlying combinatorial therapy is often not well established due to lack of understandings of the specific pathways responding to the drugs, and their temporal dynamics following each treatment. Here we present several emerging trends in harnessing properties of biological systems for the optimal design of drug combinations, including the type of drugs, specific concentration, sequence of addition and the temporal schedule of treatments. We highlight recent studies showing different approaches for efficient design of drug combinations including single-cell signaling dynamics, adaption and pathway crosstalk. Finally, we discuss novel and feasible approaches that can facilitate the optimal design of combinatorial therapy.

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“…BRAF is highly mutated in various cancers including melanoma, thyroid and colorectal cancers [30]. The most common V600E mutation renders BRAF V600E constitutively active.…”

Section: Introductionmentioning

confidence: 99%

Two is better than one; toward a rational design of combinatorial therapy

Chen

Lahav

2016

Current Opinion in Structural Biology

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“…Moreover, patients undergoing BRAF inhibitor therapy develop resistance against BRAF inhibitor within few months of treatment initiation (Dadu et al, 2015;Kim et al, 2013;Rahman et al, 2014b). The reasons for BRAF inhibitor resistance had been investigated and found that most of the BRAF inhibitor resistance happened due to reactivation of ERK proliferationsurvival kinase signalling pathway and a second activation of AKT proliferation-survival kinase signalling pathway (Rahman et al, 2014b).…”

Section: Introductionmentioning

confidence: 99%

Multiple proliferation-survival signalling pathways are simultaneously active in BRAF V600E mutated thyroid carcinomas

Rahman

Salajegheh

Smith

et al. 2015

Experimental and Molecular Pathology

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“…EGFR overexpression, caused by gene mutations, could also result in abnormal signal transduction and cell growth, leading to carcinogenesis (Rahman et al, 2014). Therefore, increased EGFR expression is a strong prognostic feature of multiple tumor types, and EGFR inhibition could have substantial therapeutic benefits.…”

Section: Discussionmentioning

confidence: 99%

Effect of SNX-2112 on proliferation of esophageal cancer cells via regulation of excision repair cross-complementing 1, epidermal growth factor receptor, and p53 expression

Cy¹,

Ren²,

Yd³

2016

Genet. Mol. Res.

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ABSTRACT. SNX-2112 is a potential molecular targeted therapeutic drug against esophageal cancer (EC). However, its exact mechanism of action remains to be explained. The aim of this study was to investigate the effect of SNX-2112 on excision repair cross-complementing 1 (ERCC1), epidermal growth factor receptor (EGFR), and p53, to elucidate the mechanism of action of SNX-2112 on EC. Fresh tumor sections were surgically obtained from 65 patients with EC, and the expression of ERCC1, EGFR, and p53 was determined by immunohistochemical staining. Furthermore, the effect of SNX-2112 (0.2 µM) on the proliferation of EC-9706 cells and the expression of ERCC1, EGFR, and p53 in these cells were analyzed by a cell proliferation assay and western blot, respectively. We observed a significant decrease and increase in ERCC1 (P = 0.001) and p53 (P = 0.043) expression, respectively, and no significant difference in EGFR (P = 0.59) expression, with the TNM stage of EC, which suggested that ERCC1 and p53 could be potential markers for the TNM stage of EC. We also observed a significant increase in ERCC1 expression, and decrease in p53 and EGFR expression, in EC-9706 cells treated with SNX-2112 (P < 0.05), indicating the regulation of EC by SNX-2112. Furthermore, SNX-2112 treatment induced a significant decrease in the proliferation of EC-9706, which confirmed the function of SNX-2112. In summary, SNX-2112 inhibits the proliferation of EC cells by regulating the expression of ERCC1, EGFR, and p53.

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BRAF Inhibitor Therapy for Melanoma, Thyroid and Colorectal Cancers: Development of Resistance and Future Prospects

Cited by 34 publications

References 151 publications

Two is better than one; toward a rational design of combinatorial therapy

Two is better than one; toward a rational design of combinatorial therapy

Multiple proliferation-survival signalling pathways are simultaneously active in BRAF V600E mutated thyroid carcinomas

Effect of SNX-2112 on proliferation of esophageal cancer cells via regulation of excision repair cross-complementing 1, epidermal growth factor receptor, and p53 expression

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