Mechanisms of disease: signaling of the insulin-like growth factor 1 receptor pathway--therapeutic perspectives in cancer.
The insulin-like growth factor 1 (IGF1) signaling pathway is implicated in the development of cancer. High levels of circulating IGF1 and certain genetic polymorphisms of IGF1 and IGFBP3 are associated with an increased risk of several common cancers. The IGF1 receptor (IGF1R) has been shown to be expressed in a wide range of tumors, and IGF1R signaling is crucial for tumor transformation and the survival of malignant cells. Several monoclonal antibodies and small-molecule inhibitors have been tested in preclinical studies and early-phase clinical studies. IGF1R signaling interferes with numerous growth factors and receptors such as VEGF and EGFR. In the experimental system, IGF1R signaling has been found to correlate with resistance to therapies based on the inhibition of EGFR and HER2. This Review highlights the most relevant studies in this exciting area of research, focusing in particular on the role of IGF1R in resistance to other receptor-targeted therapies for cancer.
Tao
Yungan
Y
Institute Gustave-Roussy and the Department of Radiation Oncology of Cancer Hospital, Fu Dan University, Shanghai, China.
Pinzi
Valentina
V
Bourhis
Jean
J
Deutsch
Eric
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D011110:Polymorphism, Genetic; D020239:Receptor Cross-Talk; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1