title: Prediction of anti-angiogenesis escape.
abstract: Many clinical trials have demonstrated the benefit of anti-angiogenesis therapy in the treatment of gynecologic cancer. However, these benefits have often been in terms of progression-free rather than overall survival and in some cases, the magnitude of benefit demonstrated in the pivotal phase 3 trials has been disappointing when compared with the percentage of patients who responded in earlier phase 2 trials. Two potential explanations for this are the current inability to stratify patients according to chance of benefit and the development of resistance mechanisms within the tumor. In this article, we review the prediction of response and the proposed resistance and escape mechanisms involved in anti-angiogenesis therapy, including the up-regulation of alternative proangiogenic pathways, vascular co-option, and resistance to hypoxia. These insights may offer a personalized strategy for anti-angiogenesis therapy and help us to consider the best selection of other therapies that should be combined with anti-angiogenesis therapy to improve the outcome of patients with gynecologic cancer.
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030, USA. Electronic address: tmitamura@mdanderson.org.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mitamura
authors.affiliation: University of Edinburgh Cancer Research UK Centre, MRC IGMM, Crewe Road South, Edinburgh, EH4 2XR, UK. Electronic address: Charlie.Gourley@ed.ac.uk.
authors.forename: Charlie
authors.initials: C
authors.lastname: Gourley
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D057285:Precision Medicine
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Anti-angiogenesis therapy; Escape mechanisms; Prediction of response; Resistance