Publication Name	World Journal of Gastrointestinal Oncology
Manuscript ID	107380
Country	China

Category	Oncology
Manuscript Type	Minireviews
Article Title	Targeting SHP2: Dual breakthroughs in colorectal cancer therapy–from signaling pathway modulation to immune microenvironment remodeling
Manuscript Source	Invited Manuscript
All Author List	Pan Liu and Jia Chen
Funding Agency and Grant Number	Funding Agency Grant Number Zhejiang Provincial Natural Science Foundation for Youths QN25H160012 Zhejiang Medical and Health Science and Technology Plan 2023RC006
Corresponding Author	Jia Chen, Clinical Assistant Professor (Honorary), Pulmonary and Critical Care Medicine, Zhuji Central Hospital, Zhugong Road No.98, Zhuji 311800, Zhejiang Province, China. 13357530129@163.com
Key Words	Colorectal cancer; Protein tyrosine phosphatase SHP2; Targeted therapy; PI3K/AKT pathway; Tumor microenvironment
Core Tip	This paper summarizes the regulatory mechanisms of SHP2 in colorectal cancer (CRC) and emerging therapeutic strategies targeting SHP2. The findings demonstrated that SHP2 serves as a master oncogenic regulator in CRC pathogenesis by coordinating receptor tyrosine phosphatase-mediated signaling. Notably, SHP2 remodels the tumor immune microenvironment by modulating macrophage and T cell functions. Allosteric inhibitors of SHP2, which are characterized by high oral bioavailability and potent target specificity, are currently under evaluation in multicenter phase I/II trials. Although acquired resistance remains challenging, combination strategies, particularly immunotherapy-based treatments, demonstrated transformative potential, accelerating the transition of SHP2-targeted therapies and offering novel paradigms for personalized CRC treatment.
Citation	Liu P, Chen J. Targeting SHP2: Dual breakthroughs in colorectal cancer therapy–from signaling pathway modulation to immune microenvironment remodeling. World J Gastrointest Oncol 2025; In press

Received	2025-03-24 07:07
Peer-Review Started	2025-03-24 07:07
To Make the First Decision
Return for Revision	2025-04-03 08:51
Revised	2025-04-17 07:31
Second Decision	2025-05-30 02:43
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-05-30 06:57
Articles in Press	2025-05-30 06:57
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-5204 (online)
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