Inhibition of mutagenic translesion synthesis: A possible strategy for improving chemotherapy?

[...]mistakes introduced by TLS polymerases copying over DNA lesions introduced during the chemotherapy lead to mutations that contribute to acquired resistance. Besides the structural features of individual TLS polymerases, successful TLS also depends on interactions between these polymerases and other cellular proteins that target and choreograph their activity. [...]targeting REV1 and REV3 might not only increase killing of cancer cells but could also potentially suppress secondary malignancies and tumor relapse. [...]the effectiveness of small molecule inhibitors of TLS polymerase could be further improved by delivery systems that could target these drugs to specific tumors in cancer patients. Because protein-protein interactions are so important for TLS, drug targets for these interaction interfaces could be promising candidates for cancer therapeutics.