Restoring order at the cell cycle border: Co-targeting CDK4/6 and CDK2.

Overcoming resistance to CDK4/6 inhibitors is a major clinical challenge. In this issue of Cancer Cell, Freeman-Cook et al. study mechanisms of resistance to CDK4/6 inhibitors by employing a CRISPRa screen. They identify the cyclin E-CDK2 axis and Myc signaling as key pathways of resistance and develop PF-06873600, a selective CDK2/4/6 inhibitor.
Competing Interests: Declaration of interests R.J. receives research funding from Pfizer and Lilly and is a consultant for Carrick Therapeutics and Luminex. R.S. receives research funding from AstraZeneca, GlaxoSmithKline, Puma, Biotechnology Inc., and Gilead Sciences (to the institution); she has been a past ad hoc advisory committee member for Eli Lilly; she is a consulting/advisory committee member for Macrogenics; and she has other financial interests: UpToDate Royalties.
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