Article
TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes STK11-Mutant Tumors to Anti-PD-1 Immunotherapy.
Cancer research - 15 Oct 2025
Ahronian Leanne G, Sahu Soumyadip, Zhang Minjie, Patel Ayushi S, Geng Ke, Bhattacharya Reshmee, Falchook Gerald S, Goldman Jonathan W, Spira Alexander I, Punekar Salman R, Spigel David R, Wang Judy S, Skoulidis Ferdinandos, Stephens Janaye, Meynardie Mary, Powell Jaylen M, Lopez Alfonso, Ranieri Michela, Ploszaj Magdalena A, Tan Yi Jer, Lee Yeuan Ting, Yu Yi, Deng Jiehui, Chen Ting, McCarren Patrick, Tsai Alice, Hussain Suleman S, Doyon Brian, Amemiya Kenjie, Ermolieff Jacques, Shahagadkar Preksha, Das Nikitha M, Flynn Lauren R, Shields Julie A, Danielczyk Laney, McMillan Brian J, Mignault Andre, Meier Samuel R, Wu Hsin-Jung, Guerin David J, Whittington Douglas A, Min Chengyin, Sienczylo Iga, Maxwell John P, DiBenedetto Heather J, Watanabe Hideo, Haines Brian B, Huang Alan, Crystal Adam, Andersen Jannik N, Wu Xinyuan, Wong Kwok-Kin
Abstract excerpt
Patients with non-small cell lung cancer (NSCLC) with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti-PD-1. In this study, we conducted an in vivo CRISPR screen that identified histone deacetylase 1 as a target to reverse anti-PD-1 resistance driven by loss of STK11 and developed TNG260, a potent small-molecule inhibitor of the CoREST complex with selectivity...
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