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Mechanisms of GIP in inhibiting cancer growth: Updates and perspectives
Aixin Wang1, Xinyu Ye1, G J Mizejewski2
1National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, PR China; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Abstract:
Alpha-fetoprotein (AFP), an embryonic protein, has long been recognized as a biomarker for hepatocellular carcinoma and various other malignancies. While the intact form of AFP promotes tumor growth, its derived peptide fragments, termed growth inhibitory peptides (GIPs), exhibit potent anticancer properties. GIPs inhibit tumor proliferation, migration, invasion and angiogenesis through multiple mechanisms, including MAPK and FAK/PI3K/Akt signaling inhibition, disruption of extracellular matrix-integrin interactions, regulation of cyclins and endogenous cyclins inhibitors, and ion channel blockade. Despite these promising effects, several challenges hinder the clinical translation of GIPs, including incomplete understanding of their molecular mechanisms, limited pharmacokinetic profiles, and insufficient in vivo stability. This review provides a comprehensive analysis of GIPs' physicochemical properties, biological activities, and their multifaceted anticancer mechanisms. Furthermore, it addresses current limitations and outlines strategies for future research, such as molecular optimization, targeted delivery, and improved preclinical validation. By synthesizing existing evidence, this review aims to establish a foundational framework for the development of GIPs as novel therapeutic peptides in oncology.
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