Department of Pharmacology, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology (SRMIST), Mahatma Gandhi Rd, Potheri, SRM Nagar, Kattankulathur, Tamil Nadu, INDIA
Correspondence:
Dr. Indumathi Prabath
Associate Professor, Department of Pharmacology, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, Mahatma Gandhi Rd, Potheri, SRM Nagar, Kattankulathur-603202, Tamil Nadu, INDIA
Email: indumatp2@srmist.edu.in
Aim/Background: The function of Src Homology 2-containing Phosphotyrosine Phosphatase (SHP2) in oncology has been established with elaborate systematic reviews. Similarly, researchers have identified its role in non-cancerous conditions such as idiopathic pulmonary fibrosis, acute lung injury, cardiac fibrosis, systemic sclerosis, osteoarthritis, systemic lupus erythematosus, etc., but systematic reviews are limited. Hence, this systematic review seeks to compile the existing preclinical literature on the impacts of SHP2 in non-cancer disease conditions.
Materials and Methods: This review adheres to the Preferred PRISMA (Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. This search was made across 6 databases, such as Medline, PubMed, EMBASE, Cochrane Collaboration Library, PubMed Central, and Google libraries, for the original research publications examining the preclinical impact of SHP2 on non-cancer diseases.
Results: A total of 76 articles were identified, and after eliminating unsuitable articles, 15 articles were included in the qualitative synthesis. They were sourced from four different countries, with 10 articles (66.6%) attributed to researchers from China, followed by 2 articles (13.3%) each from the United States and South Korea, and 1 article (6.7%) from France. Among the 15 articles, 11 (73.3%) concentrated on diseases, while 4 (26.7%) examined the inhibitory effects of SHP2 and its expression in treatment strategies. Most studies utilized SHP099 as the SHP2 inhibitor, while only one study employed a small-molecule inhibitor targeting Y279C SHP2 (compound 99).
Conclusion: The present review emphasizes the potential of SHP2 as a therapeutic target for non-cancerous diseases, acting as both an agonist and antagonist depending on the specific deficiency or overexpression linked to the condition. The insights regarding SHP2 are encouraging, prompting this study to call for additional research, especially in the realm of clinical trials. This is particularly relevant for diseases such as idiopathic pulmonary fibrosis, where lung transplantation is the only available treatment, yet it frequently remains out of reach for many individuals due to prohibitive costs and uncertain accessibility.
Keywords: MEK pathway, Non-cancer diseases, SHP2, SHP099, Src homology 2-containing phosphotyrosine phosphatase.
How to cite this article: Raja S, Rahangan A, Prabath I, Shobana N, Rani J. Preclinical Advances in SHP2 Beyond Oncology: An In-Depth Systematic Review of Emerging Preclinical Evidence for SHP2 Treatment in Non-Cancer Applications: A Ten-Year Overview. Int J Drug Deliv Technol. 2026;16(6s): 642-653; DOI: 10.25258/ijddt.16.6s.90
Source of support: None
Conflict of interest: None