The type I insulin-like growth factor receptor pathway: a key player in cancer therapeutic resistance.
The insulin-like growth factor (IGF) ligands stimulate cellular proliferation and survival by activating the type I insulin-like growth factor receptor (IGF-IR). As a result, the IGF signaling system is implicated in a number of cancers, including those of the breast, prostate, and lung. In addition to mitogenic and anti-apoptotic roles that may directly influence tumor development, IGF-IR also appears to be a critical determinant of response to numerous cancer therapies. This review describes the role of the IGF-IR pathway in mediating resistance to both general cytotoxic therapies, such as radiation and chemotherapy, and targeted therapies, such as tamoxifen and trastuzumab. It concludes with a description of approaches to target IGF-IR and argues that inhibition of IGF signaling, in conjunction with standard therapies, may enhance the response of cancer cells to multiple modalities.
Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Angelo J
AJ
Casa
Robert K
RK
Dearth
Beate C
BC
Litzenburger
Adrian V
AV
Lee
Xiaojiang
X
Cui
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000628:therapy; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011471:Prostatic Neoplasms / Q000628:therapy; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D015398:Signal Transduction; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D020845:Selective Estrogen Receptor Modulators; D000077267:Fulvestrant; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D017526:Receptor, IGF Type 1