Work

Protein phosphatase 2A as a therapeutic target in pancreatic cancer: past insights, recent advances, and future directions

Year: 2025

Type: review

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an 8% five-year survival rate. KRAS, the major oncogenic driver, triggers several phosphorylation cascades, making phosphatases, particularly protein phosphatase 2A (PP2A), which accounts for 50–70% of cellular phosphatase activity, a critical regulator. Through association with multiple regulatory subunits, PP2A modulates both tumor-suppressive and tumor-promoting functions. The tumor-suppressive function is often inhibited in PDAC by endogenous inhibitors like SET and CIP2A, which are frequently upregulated. This review examines the multifaceted roles of PP2A in PDAC, with a focus on its published roles in KRAS-MYC signaling, DNA damage response, and epithelial-to-mesenchymal transition, as well as current and emerging therapeutic strategies aimed at modulating PP2A activity.

Source: Current Opinion in Physiology

DOI: 10.1016/j.cophys.2025.100849

Authors: Vidhi M Shah, Rosalie C Sears

Institutions: Oregon Health & Science University, OHSU Knight Cancer Institute

Language: English

Topic: Pancreatic and Hepatic Oncology Research

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,500