Anticancer efficacy of KRASG12C inhibitors is potentiated by PAK4 inhibitor KPT9274 in preclinical models of KRASG12C mutant pancreatic and lung cancers.
Husain Yar KhanMisako NagasakaAmro AboukameelOsama AlkhaliliMohammed H UddinSahar BannouraYousef MzannarIbrahim AzarEliza BealMiguel TobonSteve KimRafic BeydounErkan BalogluWilliam SenapedisBassel El-RayesPhilip A PhilipRamzi M MohammadAnthony F ShieldsMohammed Najeeb Al-HallakAsfar S AzmiPublished in: bioRxiv : the preprint server for biology (2023)
KRASG12C inhibitors demonstrate limited durable response in patients with KRASG12C mutations. In this study, combining PAK4 inhibitor KPT9274 with KRASG12C inhibitors has resulted in potent antitumor effects in preclinical cancer models of PDAC and NSCLC. Our results bring forward a novel combination therapy for cancer patients that do not respond or develop resistance to KRASG12C inhibitor treatment.