Patients with small cell lung cancer (SCLC) have limited therapeutic options and a poor prognosis. Alkylating-based chemotherapy — which causes DNA damage to prevent cell division — initially improves survival in SCLC but has toxic side effects and cancers eventually develop resistance. Newer platinum-based chemotherapy has lower toxicity, but cancers still become resistant. In a new study, Pawel Mazur, Ph.D., and colleagues performed pharmacologic and proteomics screens to identify the protein methyltransferase SMYD3 and its new substrate RNF113A as previously unrecognized mediators of resistance to alkylating agents. Using in vitro and in vivo models, the researchers demonstrated that combination therapy with a SMYD3 inhibitor and an alkylating agent effectively stopped tumor progression compared to either treatment alone. This finding has broad implications for combining SMYD3 inhibitors with alkylating-based chemotherapy to improve patient responses.
Adding targeted therapy improves chemotherapy responses in small cell lung cancer models
