INK4 tumor suppressor proteins mediate resistance to CDK4/6 kinase inhibitors

Li Q, Jiang B, Guo J, Shao H, Del Priore IS, Chang Q, Kudo R, Li Z, Razavi P, Liu B, Boghossian AS, Rees MG, Ronan MM, Roth JA, Donovan KA, Palafox M, Reis-Filho JS, de Stanchina E, Fischer ES, Rosen N, Serra V, Koff A, Chodera JD, Gray NS, and Chandardlapaty S
Cancer Discovery} 12:356, 2022 [DOI]

We demonstrate CDK6 causes drug resistance by binding INK4 proteins, and develop bifunctional degraders conjugating palbociclib with E3 ligands to overcome this mechanism of resistance.