KRAS mutation: The booster of pancreatic ductal adenocarcinoma transformation and progression

Zining Zhang; Heng Zhang; Xiang Liao; Hsiang-I Tsai

doi:10.3389/fcell.2023.1147676

KRAS mutation: The booster of pancreatic ductal adenocarcinoma transformation and progression

Front Cell Dev Biol. 2023 Apr 20:11:1147676. doi: 10.3389/fcell.2023.1147676. eCollection 2023.

Authors

Zining Zhang^{1

2}, Heng Zhang^{1

2}, Xiang Liao^{1

2}, Hsiang-I Tsai^{1

2}

Affiliations

¹ Institute of Medical Imaging and Artificial Intelligence, Jiangsu University, Zhenjiang, China.
² Department of Medical Imaging, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It has a poor response to conventional therapy and has an extremely poor 5-year survival rate. PDAC is driven by multiple oncogene mutations, with the highest mutation frequency being observed in KRAS. The KRAS protein, which binds to GTP, has phosphokinase activity, which further activates downstream effectors. KRAS mutation contributes to cancer cell proliferation, metabolic reprogramming, immune escape, and therapy resistance in PDAC, acting as a critical driver of the disease. Thus, KRAS mutation is positively associated with poorer prognosis in pancreatic cancer patients. This review focus on the KRAS mutation patterns in PDAC, and further emphases its role in signal transduction, metabolic reprogramming, therapy resistance and prognosis, hoping to provide KRAS target therapy strategies for PDAC.

Keywords: KRAS mutation; PDAC; metabolic reprogramming; phosphokinase; poorer prognosis; therapy resistance.

Publication types

Review

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (82071984, 82001698, 82272066), Project of Social Development Guiding Science and Technology of Zhen-jiang City (FZ2021055), Infectious and Inflammatory Radiology Committee of Jiangsu Re-search Hospital Association (GY202205), Jinshan talents in the medical field of Zhenjiang (JSYCBS202101), and Postgraduate Innovation Project of Jiangsu Province (SJCX22_1878).