Targeting the type 1 insulin-like growth factor receptor as anti-cancer treatment.
The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed by many tumors, and mediates growth, motility and protection from apoptosis. Inhibition of IGF1R expression or function has been shown to block tumor growth and metastasis, and enhance sensitivity to cytotoxic drugs and irradiation. Thus the IGF1R is a highly promising anti-cancer treatment target. This review describes approaches to target the IGF1R using antibodies, small molecule inhibitors of the IGF1R tyrosine kinase, and molecular agents such as antisense and small interfering RNAs. Problems for the clinical introduction of this approach may include toxicity due to normal tissue IGF1R expression and cross-reactivity with the insulin receptor. The next few years will see clinical trials of IGF1R targeting, which offers genuine potential to inhibit tumor growth and chemoresistance in patients with cancer.
Bohula
Erin A
EA
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, Oxford, UK.
Playford
Martin P
MP
Macaulay
Valentine M
VM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D034622:RNA Interference / Q000502:physiology; D016372:RNA, Antisense / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D016372:RNA, Antisense; D017526:Receptor, IGF Type 1