Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer.

ABSTRACT: Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage resp

SUBMITTER: Rajurkar M 

PROVIDER: S-EPMC9167735 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature