Split Cyclin-Dependent Kinase 4/6–Retinoblastoma 1 Axis in Pancreatic Cancer

• Main Authors: Xing Huang, Gang Zhang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-11-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: CDK4/6; combination therapy; pancreatic cancer; precise treatment; prognosis; Rb1
• Online Access: https://www.frontiersin.org/articles/10.3389/fcell.2020.602352/full

Drugs targeting the cyclin-dependent kinase 4/6 (CDK4/6)–retinoblastoma 1 (RB1) axis have shown efficacy against multiple solid cancers, but their therapeutic potential in pancreatic cancer remains poorly defined. A recent report proposed that a “tailored” combination of first-line and second-line CDK4-targeting drugs would hold promise for pancreatic cancer treatment. Indeed, this therapeutic strategy exhibited significantly suppressive effects on pancreatic cancer patient-derived cell lines and tumor tissue in vitro. However, the study neglected immune involvement and the influence of CDK6 and RB1 in CDK4 inhibition-based treatment. Herein, we reveal multiple new facets of the CDK4/6–RB1 axis in pancreatic cancer, highlighting the complexity of this signaling axis for future prognostic and therapeutic targeting.