Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer

Mohanty, Atish; Nam, Arin; Srivastava, Saumya; Jones, Jeff; Lomenick, Brett; Singhal, Sharad S.; Guo, Linlin; Cho, Hyejin; Li, Aimin; Behal, Amita; Mirzapoiazova, Tamara; Massarelli, Erminia; Koczywas, Marianna; Arvanitis, Leonidas D.; Walser, Tonya; Villaflor, Victoria; Hamilton, Stanley; Mambetsariev, Isa; Sattler, Martin; Nasser, Mohd W.; Jain, Maneesh; Batra, Surinder K.; Soldi, Raffaella; Sharma, Sunil; Fakih, Marwan; Mohanty, Saswat Kumar; Mainan, Avijit; Wu, Xiwei; Chen, Yihong; He, Yanan; Chou, Tsui-Fen; Roy, Susmita; Orban, John; Kulkarni, Prakash; Salgia, Ravi

doi:10.1126/sciadv.ade3816

Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer

Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin β4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in …