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Vemurafenib, BRAF inhibitor, Resistance in BRAFV600E Positive Thyroid Cancer cell lines

ABSTRACT: We report the application of single-molecule-based sequencing technology for high-throughput profiling of RNAs in BRAFV600E+ thyroid cancer cell lines 8505C and WRO. We generated genome-wide transcriptome maps of 8505C and WRO cells after vemurafenib, BRAF inhibitor, treatment. In addition, we generated genome-wide transcriptome maps of clonally selected vemurafenib-resistant 8505C and WRO cells with or without vemurafenib treatment. Negative control treatment was 0.1% of dimethy solfoxide (DMSO), the diluent used to resuspend vemurafenib. The treatment regine of vemurafenib was 2 µM concentration for 24 hours. We find that both inducible response to BRAFi and acquired BRAFi resistance in thyroid cancer cells showed significant activation of the JAK/STAT pathway. Our study demonstrates that the JAK/STAT-signaling pathway is activated as thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer and potentially in other malignancies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178267 | GEO | 2023/02/16

REPOSITORIES: GEO

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Giani2019 - Computational modeling to predict MAP3K8 effects as mediator of resistance to vemurafenib in thyroid cancer stem cells

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