CHINESE JOURNAL OF MEDICINAL GUIDE >
Research Progress on the Role of HIPK2 in Colorectal Cancer
Received date: 2025-06-25
Revised date: 2025-08-28
Accepted date: 2026-03-18
Online published: 2026-03-19
Colorectal cancer （CRC） is one of the most common malignancies of the digestive system worldwide， characterized by high incidence， high mortality， and high recurrence. Although multimodal treatments including surgery， chemotherapy， targeted therapy， and immunotherapy have achieved certain advances， the tumor’s molecular heterogeneity， associated drug resistance， and high relapse rate still seriously compromise clinical outcomes. Therefore， identifying novel molecular regulatory mechanisms and therapeutic targets has become a central focus of basic and translational CRC research. Homeodomain-Interacting Protein Kinase 2 （HIPK2） is a highly conserved serine/threonine protein kinase that plays a key regulatory role in the development and progression of various cancers. HIPK2 exerts notable tumor-suppressive functions by activating p53 and modulating apoptosis and DNA damage-repair pathways， and its reduced expression is often closely associated with tumor progression， therapeutic resistance， and poor prognosis. As a multifunctional tumor suppressor， HIPK2 regulates cancer cell growth and apoptosis in response to anticancer agents and negatively influences pathways involved in tumor progression and chemoresistance. Given HIPK2’s pivotal role in CRC， the development of small-molecule HIPK2 agonists has emerged as an attractive yet challenging therapeutic strategy. This review summarizes HIPK2’s structure and function， its expression in CRC， its effects on CRC cell behavior， and its potential as a therapeutic target for CRC.
Key words： Colorectal cancer; HIPK2; Therapeutic target; Small molecule agonist
CAO Yuwen, SHEN Xingjie
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Research Progress on the Role of HIPK2 in
Colorectal Cancer
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