CDK4/6 Inhibitors

Cyclin-dependent kinases 4 & 6 inhibitor, Palbociclib (Ibrance), is FDA-approved for ER-positive and HER2- negative breast cancer. Cyclin-dependent kinases are reg- ulators of cell cycle and cell division and are important for progression of some cancers. In a study published by Goel, et al. in Nature, August 2017, they demonstrate that inhibitors of CDK4/6 can promote anti-tumor immunity. One mecha- nism was by increasing retroviral elements within cancers that resulted in increased double-stranded RNA. This caused an increase in interferons and antigen presentation. In addition, CDK4/6 inhibitors decrease T regulatory cells. These effects result in an increase in the cytotoxic T cell response (attack- ing T cells). Other studies, such as “The CDK4/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenviron- ment and Enhances the Efficacy of PD-L1 Checkpoint Block- age” by Schaer, et al., support the idea that a combination ofCDK4/6 inhibitors with immunotherapy, such as PD-1/PD-L1 inhibitors, should have good synergy. The ability to convert a “cold” tumor to a “hot/inflamed” one is a very key area that is lacking in traditional immune checkpoint therapy, leading to failure. Though the human data is still lacking, patients who are getting CDK4/6 inhibitors, should certainly look into the option of getting immunotherapy at the same time.

Reference: Jason R. Williams, 15 Oct 2019, The Immunotherapy Revolution: The Best New Hope For Saving Cancer Patients’ Lives,