Abstract
Identification of mechanisms underlying sensitivity and response to targeted therapies, such as the BRAF inhibitor vemurafenib, is critical in order to improve efficacy of these therapies in the clinic and delay onset of resistance. Glycolysis has emerged as a key feature of the BRAF inhibitor response in melanoma cells, and importantly, the metabolic response to vemurafenib in melanoma patients can predict patient outcome. Here, we present a multiparameter genome-wide siRNA screening dataset of genes that when depleted improve the viability and glycolytic response to vemurafenib in BRAFV600 mutated melanoma cells. These datasets are suitable for analysis of genes involved in cell viability and glycolysis in steady state conditions and following treatment with vemurafenib, as well as computational approaches to identify gene regulatory networks that mediate response to BRAF inhibition in melanoma.
Highlights
Background & SummaryOncogene targeted therapies have significantly improved clinical outcomes for cancer patients, response to these therapies is limited by development of resistance
In the setting of BRAF mutant melanoma, inhibition of BRAF signalling results in oncogenic network rewiring that allows cellular adaptation and drug tolerance, and this often precedes development of resistance. In both preclinical and clinical studies of melanoma, drug induced adaptation reprograms metabolism, and importantly, sensitivity to inhibitors of mutated BRAFV600 correlates with glycolytic response in pre-clinical[1] and clinical studies[2]
Alterations in cellular metabolism is a hallmark of cancer, how targeted therapy reprograms metabolism and the role this plays during the adaptive response and development of resistance has received much less attention
Summary
Background & SummaryOncogene targeted therapies have significantly improved clinical outcomes for cancer patients, response to these therapies is limited by development of resistance. Deconvolution of 400 candidate SMARTPools - 4x siRNA duplexes per gene - Lactate and viability assays used in primary screen - biological reproducibility of phenotypes - reproducibility of gene knockdown www.nature.com/scientificdata
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