Article
KEAP1 and STK11/LKB1 alterations enhance vulnerability to ATR inhibition in KRAS mutant non-small cell lung cancer.
Cancer cell - 11 Aug 2025
Galan-Cobo Ana, Vokes Natalie I, Qian Yu, Molkentine David, Ramkumar Kavya, Paula Alvaro G, Pisegna Marlese, McGrail Daniel J, Poteete Alissa, Cho Sungnam, Do Minh Truong, Karimi Amirali, Kong Yifan, Solanki Anisha, Karmokar Ankur, Floc'h Nicolas, Hughes Adina, Sargeant Rebecca, Young Lucy, Shen Li, Kar Gozde, Keshvani Caezaan, Arrechedera Claudio, Hernandez Sharia, Schlacher Katharina, Wang Jing, Iyer Sonia, Conway James, Keddar Mohamed Reda, Milo Marta, de Toma Ilario, Critchlow Susan E, Barrett J Carl, Cosaert Jan, Lau Alan, Valge-Archer Viia, Byers Lauren A, Barry Simon T, Heymach John V
Abstract excerpt
KRAS mutations frequently co-occur with alterations in STK11/LKB1 and/or KEAP1, defining an aggressive subset of lung cancers resistant to immuno- and chemotherapy. While LKB1 loss is associated with vulnerability to DNA damage response-based therapies, the impact of KEAP1 alterations remains unknown. We demonstrate that KEAP1-NRF2 pathway drives a compensatory modulation of ATR-CHK1 signaling, enhancing...
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