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VEGF blockade enhances the antitumor effect of BRAFV600E inhibition

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE69754 | GEO | 2016/12/19

SECONDARY ACCESSION(S): PRJNA286655

REPOSITORIES: GEO

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VEGF blockade enhances the antitumor effect of BRAFV600E inhibition.

Project description:The development of resistance remains a major obstacle to long-term disease control in cancer patients treated with targeted therapies. In BRAF-mutant mouse models, we demonstrate that although targeted inhibition of either BRAF or VEGF initially suppresses the growth of BRAF-mutant tumors, combined inhibition of both pathways results in apoptosis, long-lasting tumor responses, reduction in lung colonization, and delayed onset of acquired resistance to the BRAF inhibitor PLX4720. As well as inducing tumor vascular normalization and ameliorating hypoxia, this approach induces remodeling of the extracellular matrix, infiltration of macrophages with an M1-like phenotype, and reduction in cancer-associated fibroblasts. At the molecular level, this therapeutic regimen results in a de novo transcriptional signature, which sustains and explains the observed efficacy with regard to cancer progression. Collectively, our findings offer new biological rationales for the management of clinical resistance to BRAF inhibitors based on the combination between BRAFV600E inhibitors with anti-angiogenic regimens.

| S-EPMC5286370 | biostudies-literature

VEGF blockade enhances the antitumor effect of BRAFV600E inhibition (mouse)

Project description:In this work we investigated the combined effects of the BRAF inhibition and of the VEGF blockade in a preclinical model of melanoma. The purpose of this dataset was to examine the transcriptional responses of a A375 xenograft model to PLX472 and bevacizumab, either as single agents or as combination therapy. We performed species-specific analysis of gene expression to discriminate the effects of the different therapeutic regimens on tumor cells (human) and stromal microenvironment (mouse). Here, Illumina Mouse BeadChips were used to profile the transcriptome after 12 days treatment. We reported that dispensing the dual treatment is more efficient than the single compounds and the occurrence of resistance by modifying the tumor genetic programs regulating myeloid cells recruitment and extracellular matrix remodeling.

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VEGF blockade enhances the antitumor effect of BRAFV600E inhibition (human)

Project description:In this work we investigated the combined effects of the BRAF inhibition and of the VEGF blockade in a preclinical model of melanoma. The purpose of this dataset was to examine the transcriptional responses of a A375 xenograft model to PLX472 and bevacizumab, either as single agents or as combination therapy. We performed species-specific analysis of gene expression to discriminate the effects of the different therapeutic regimens on tumor cells (human) and stromal microenvironment (mouse). Here, Illumina Human BeadChips were used to profile the transcriptome after 12 days treatment. We reported that dispensing the dual treatment is more efficient than the single compounds and the occurrence of resistance by modifying the tumor genetic programs regulating myeloid cells recruitment and extracellular matrix remodeling.

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VEGF blockade enhances the antitumor effect of BRAFV600E inhibition

Project description:VEGF blockade enhances the antitumor effect of BRAFV600E inhibition

| PRJNA286655 | ENA

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