CDK4/6 Inhibitors in Pancreatobiliary Cancers: Opportunities and Challenges

SIMPLE SUMMARY: Pancreatobiliary cancers are a group of malignancies affecting the pancreas and biliary tract and are among the cancers with the lowest survival rate. Current first-line treatments only offer a modest increase in overall survival, and there is an urgent need to develop new therapeutic strategies. Emerging evidence suggests cyclin-dependent kinase 4/6 (CDK4/6) inhibitors as an attractive therapeutic strategy for solid cancers, and here, we summarize the current knowledge and exploration of their therapeutic potential in the most common pancreatobilliary cancers, cholangiocarcinoma and pancreatic ductal adenocarcinoma. ABSTRACT: Existing treatment strategies for pancreatobiliary malignancies are limited. Nowadays, surgery is the only path to cure these types of cancer, but only a small number of patients present with resectable tumors at the time of diagnosis. The notoriously poor prognosis, lack of diverse treatment options associated with pancreaticobiliary cancers, and their resistance to current therapies reflect the urge for the development of novel therapeutic targets. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as an attractive therapeutic strategy in a number of cancers since their approval for treatment in patients with ER+/HER- breast cancer in combination with antiestrogens. In this article, we discuss the therapeutic potential of CDK4/6 inhibitors in pancreatobiliary cancers, notably cholangiocarcinoma and pancreatic ductal adenocarcinoma.