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.
Casa
Angelo J
AJ
Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Dearth
Robert K
RK
Litzenburger
Beate C
BC
Lee
Adrian V
AV
Cui
Xiaojiang
X
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