Enhancing sensitivity of triple‐negative breast cancer to DNA‐damaging therapy through chemical inhibition of the m6A methyltransferase METTL3

In breast cancer, METTL3 knockdown markedly suppresses proliferation, invasiveness, and metastasis [ 4]. [...]METTL3 inhibition is proposed as a therapeutic approach for breast cancer. [...]METTL3 knockdown reduces DNA repair activity and sensitizes cancer cells to genotoxic drugs [ 7, 8]. Platinum-based chemotherapeutic agents and PARP inhibitors, such as olaparib, showed mostly favourable responses in TNBC harboring BRCA1/2 mutations [ 5]. Since STM2457 downregulated genes involved in the DNA repair pathway, we hypothesized that it may reduce homologous recombination (HR) proficiency also in TNBC cells that are wild-type for BRCA1/2. [...]we observed substantial and consistent increase in DNA damage in response to combined treatments (Supplementary Figure S7A-B).