Targeting IGF-1 signaling pathways in gynecologic malignancies.

INTRODUCTION: The signaling pathways of the insulin-like growth factors (IGF) have been implicated in the etiology of a number of epithelial neoplasms including prostate, breast, colon and more recently, gynecologic cancers. The insulin-like growth factor-1 receptor (IGF-1R) is expressed in most transformed cells, where it displays potent anti-apoptotic, cell-survival and potentially, transforming activities. IGF-1R expression and activation are typical hallmarks associated with tumor initiation and progression. Multiple approaches have been used to abrogate IGF-1R signaling for targeted cancer therapy including antibodies and small molecule tyrosine kinase inhibitors. These novel IGF-1R targeting agents have produced significant experimental and clinical results in many cancers and generated considerable optimism in the field of cancer therapy. AREAS COVERED: The authors will review important research advances regarding the role of the IGF axis in cancer, particularly preclinical and clinical studies in cervical, uterine and ovarian cancers. The significance of tumor expression and circulating levels of the IGF pathway as well as targeting therapies of the IGF axis in the gynecologic cancers will be discussed. EXPERT OPINION: Accumulating data confirm that the IGF-1R pathway has an important role in gynecologic cancers and in vivo and in vitro studies have shown a significant impact of IGF-1R targeted therapies in these malignancies, mainly ovarian and endometrial cancers. Currently, ongoing preclinical and clinical trials are evaluating the efficacy of IGF-1R targeting. A better understanding of the complex mechanisms underlying the regulation of the IGF system will improve the ability to develop effective treatment modalities for these malignancies.