Emerging cell-cycle inhibitors for pancreatic cancer therapy

Abstract

Introduction: Patients with pancreatic cancer (PC) present with advanced disease that is lethal and notoriously difficult to treat. The research focused initially on combining cytotoxic therapies with gemcitabine, and over the past decade, a large number of studies have been published that aimed to target the molecular abnormalities implicated in pancreatic tumor growth.

Areas covered: The cell cycle is a tightly regulated series of events that governs cell replication and division. Deregulation of cell cycle kinases have been implicated in PC tumorigenesis. In this review, we discuss the potential and limitations of current cyclin-kinase inhibitors. We also summarize progress in evaluating other mitotic kinase inhibitors and novel cell-cycle kinase inhibitors as potential therapeutic agents in PC.

Expert opinion: While the successful development and approval of cell-cycle inhibitors for PC therapy remains unresolved, pre-clinical identification of resistant mechanisms would help design better early- phase clinical trials where relevant combinations may be evaluated prior to Phase II testing. The authors believe that cell-cycle kinases are important anti-cancer targets that operate in collaboration with other oncogenes intimately involved in uncontrolled tumor proliferation and by providing a unique, targeted, and complimentary anti-cancer mechanism, expand the available armamentarium against PC.

Keywords::

• aurora kinase
• cell cycle inhibitors
• cyclin dependent kinase inhibitors
• flavopiridol
• MK-1775
• molecular targeted therapy
• pancreatic cancer
• polo-like kinase

Notes