IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights

• Published in: Molecular cancer Vol. 16; no. 1; p. 6
• Main Authors: Li, Heming, Batth, Izhar Singh, Qu, Xiujuan, Xu, Ling, Song, Na, Wang, Ruoyu, Liu, Yunpeng
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.01.2017; BioMed Central
• Subjects: Antineoplastic Agents - pharmacology; Cellular signal transduction; Clinical Trials as Topic; Drug resistance; Drug Resistance, Neoplasm - drug effects; Epithelial-Mesenchymal Transition - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; Insulin-like growth factor 1; Metastasis; Molecular Targeted Therapy; Neoplasms - drug therapy; Neoplasms - metabolism; Receptors, Somatomedin - metabolism; Review; Signal Transduction - drug effects; Therapy; IGF-I; Metastasis; IGF-IR; EMT
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-016-0576-5

The insulin-like growth factor-I (IGF-I) signaling induces epithelial to mesenchymal transition (EMT) program and contributes to metastasis and drug resistance in several subtypes of tumors. In preclinical studies, targeting of the insulin-like growth factor-I receptor (IGF-IR) showed promising anti-tumor effects. Unfortunately, high expectations for anti-IGF-IR therapy encountered challenge and disappointment in numerous clinical trials. This review summarizes the regulation of EMT by IGF-I/IGF-IR signaling pathway and drug resistance mechanisms of targeting IGF-IR therapy. Most importantly, we address several factors in the regulation of IGF-I/IGF-IR-associated EMT progression that may be potential predictive biomarkers in targeted therapy.