Resistance to paclitaxel is associated with a variant of the gene BCL2 in multiple tumor types.

ABSTRACT: Paclitaxel, the most commonly used form of chemotherapy, is utilized in curative protocols in different types of cancer. The response to treatment differs among patients. Biological interpretation of a mechanism to explain this personalized response is still unavailable. Since paclitaxel is known to target BCL2 and TUBB1, we used pan-cancer genomic data from hundreds of patients to show that a single-nucleotide variant in the BCL2 sequence can predict a patient's response to paclitaxel. Here, we show a connection between this BCL2 genomic variant, its transcript structure, and protein abundance. We demonstrate these findings in silico, in vitro, in formalin-fixed paraffin-embedded (FFPE) tissue, and in patient lymphocytes. We show that tumors with the specific variant are more resistant to

SUBMITTER: Ben-Hamo R 

PROVIDER: S-EPMC6478919 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature