Drugs targeting cyclin-dependent kinase (CDK) 4 and CDK6 can suppress the growth and survival of neoplastic mast cells, a new study published in Cancers found. Therefore, CDK4/CDK6 inhibitors could have curative potential in advanced systemic mastocytosis (SM), which is often resistant to drug treatment.

The neoplastic mast cells, which are the hallmark of advanced SM, often express KIT D816V.

In the present study, a team of researchers led by Karoline Gleixner, MD from Ludwig Boltzmann Institute for Hematology and Oncology at the Medical University of Vienna in Austria found that knocking down the expression of CDK4 and CDK6 in a neoplastic cell line that is KIT D816V positive results in the arrest of cell growth.

They also found that drugs inhibiting CDK4 and CDK6 such as palbociclib, ribociclib, and abemaciclib suppressed the proliferation of neoplastic mast cells and arrested the cell cycle. Moreover, abemaciclib also blocked growth in a drug-resistant mast cell line.

Read more about the etiology of SM

When they used CDK4/CDK6 inhibitors together with drugs targetting KIT such as midostaurin, avapritinib, and nintedanib, growth inhibition and apoptosis were further induced in neoplastic mast cells. 

Finally, the researchers found that CDK4/CDK6 inhibitors also induced apoptosis in CD34+/CD38− stem cells in advanced SM.

“Together, CDK4/CDK6 inhibition is a potent approach to suppress the growth of neoplastic cells in [advanced SM],” the researchers wrote. “Whether CDK4/CDK6 inhibitors can improve clinical outcomes in patients with [advanced SM] remains to be determined in clinical trials.”

SM is a rare disease in which neoplastic mast cells accumulate in different parts of the body. The disease can be indolent, smoldering, with an associated hematologic neoplasm, or aggressive.

Reference

Schneeweiss-Gleixner M, Filik Y, Stefanzl G, et al. CDK4/CDK6 inhibitors synergize with midostaurin, avapritinib, and nintedanib in inducing growth inhibition in KIT D816V+ neoplastic mast cells. Cancers (Basel). 2022;23;14(13):3070. doi:10.3390/cancers14133070