Article
M1C is a druggable target for NSCLC KRAS G12C mutant tumors resistant to KRAS inhibitors.
Oncogene - 1 Oct 2026
Takamori Shinkichi, Haratake Naoki, Bhattacharya Atrayee, Ozawa Hiroki, Shigeta Keisuke, Onishi Mai, Nonaka Kentaro, Komiya Takefumi, Komatsuda Hiroki, Takenaka Tomoyoshi, Yoshizumi Tomoharu, Li Chendi, Deng Jiehui, Hata Aaron N, Wong Kwok K, Long Mark D, Kufe Donald
Abstract excerpt
Treatment of NSCLC KRAS G12C mutant tumors with the allele-selective sotorasib and adagrasib inhibitors is invariably associated with acquired resistance. The MUC1-encoded oncogenic M1C protein is necessary for self-renewal of NSCLC KRAS mutant cells. We report that treatment of NSCLC KRAS G12C cells with sotorasib induces M1C expression by a STAT1-dependent pathway. In turn, M1C drives the sotorasib resistant...
Read the complete abstract on PubMedTopics
- Humans
- Drug Resistance, Neoplasm
- Animals
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung