CDK4/6 inhibitors (CDK4/6i) are standard of care for treating hormone receptor–positive breast cancer; however, resistance to these drugs is commonly observed. The mechanisms of resistance to CDK4/6i are not well established, hampering development of more effective strategies. Li, Jiang, Guo, and colleagues identified an inducible CDK6–INK4 complex that drives resistance demonstrating that, mechanistically, INK4 blocks the CDK4/6i binding pocket, thereby promoting resistance. Development of a series of CDK4/6 degrader compounds proved effective against CDK6–INK4-expressing, CDK4/6i-resistant breast cancers in vivo, providing impetus for the development of second-generation CDK4/6i.
See article, p. 356.
Standard therapies for advanced aggressive hematologic malignancies, such as leukemias and lymphomas, have a limited effect, with patients experiencing short survival times. Kornauth, Pemovska, Vladimer, and colleagues demonstrated that therapy selection based on results from a functional test is clinically possible and effective in patients with recurrent hematologic cancers. Drug effects on single cells from real-time patient...