Inhibition of TELO2 sensitizes colorectal cancer cells to chemotherapies

Abstract

Colorectal cancer is the 2nd most killing cancer around the world. Because treatments generally involve DNA damage, high toxicity and undesirable effects are frequently observed, which lead to treatment suspension. Moreover, several resistances to chemotherapy have been reported. Therefore, the research for new therapeutic approaches has become a major challenge. In this project our aim was to test the therapeutic potential of the protein TELO2 in combination with chemotherapy in colorectal cancer. TELO2 impacts the DNA damage response by affecting the stability of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) proteins. Indeed, the three classically used chemotherapies: oxaliplatin, irinotecan and 5-fluorouracil, are based on DNA damage production. We used a HCT116 derivative cell line with an auxin-inducible degron fused the endogenous TELO2 protein. We found additive effect with oxaliplatin, and synergistic effects with low doses of irinotecan and 5-fluorouracil. These results encourage to keep on researching for alternative approaches to enhace the response-rate to colorectal cancer treatments.