Pancreatic cancer is one of the deadliest cancers with 5-year survival rate of ~ 10 percent. Late diagnosis, early metastasis, and resistance to therapeutics necessitate a better treatment approach for pancreatic cancer. Alterations in epigenetic profile through DNA and histone modifications enable tumor growth and metastasis. Evading the control of growth suppressors that regulate cell cycle is also a major hallmark of cancer pathophysiology. We aimed to study a combination therapeutic targeting histone deacetylase (HDAC) and key cell cycle regulator cyclin-dependent kinase (CDK) in pancreatic cancer. We used panobinostat, a pan-HDAC inhibitor approved for multiple myeloma and abemaciclib, an FDA-approved CDK4/6 inhibitor for breast cancer. Our preliminary in vitro data in pancreatic cancer cells depicts synergistic cytotoxicity when treated in combination. In addition, combination treatment resulted in a significant decrease in proliferation and clonogenic survival of pancreatic cancer cells. Our mechanistic studies on the effects of this potent combination on histone modifications, gene expression, and cell cycle regulation will provide insights on drug synergy in pancreatic cancer cells. The results of our in vitro studies show that combining drugs that pharmacologically target two critical aspects of pancreatic cancer proliferation has a high potential for treating this lethal disease and as such merits further investigation.
This research was supported by an award from the National Institute of General Medical Sciences of the National Institutes of Health under Award Number SC2GM125550 and by funds from the College of Pharmacy and Health Sciences, St. Johnamp;rsquo;s University, NY.
