The cyclin don’t stop.

Inhibiting the PD-L1 axis is probably the most game-changing cancer treatment in the past 10 years. Unfortunately, a lot of patients just don’t respond at all, and our only predictor of response seems to be the extent of tumor PD-L1 expression. A new study in Nature describes a mechanism by which cyclin-dependent kinases (CDK) 4 and 6 regulate the abundance of PD-L1 expression. Using mouse models, the authors show that inhibiting CDK4/6 resulted in increased expression of PD-L1. Furthermore, therapeutically combining CDK4/6 inhibition with PD-L1 inhibition resulted in enhanced tumor kill and improved mouse survival. This all supports the hypothesis that giving CDK4/6 inhibitors could increase PD-L1 expression--thereby increasing PD-L1 inhibitor efficacy--in patients with low-level expression. CDK4/6 inhibition has already debuted as a first-line treatment option for advanced hormone-receptor positive breast cancer, and this data means it may be diversifying its indications as broadly as PD-L1 inhibitors. Whoa.