Abstract
Simple SummaryAngiogenesis, defined as the abnormal development of new blood vessels in cancer, is a key component of cancer development. Clinical trials have proven that angiogenesis blockers can be effective in halting cancer growth across numerous types of gynecologic cancers. This review discusses the mechanisms of angiogenesis in gynecologic cancers, current practices and areas for development.Since the discovery of angiogenesis and its relevance to the tumorigenesis of gynecologic malignancies, a number of therapeutic agents have been developed over the last decade, some of which have become standard treatments in combination with other therapies. Limited clinical activity has been demonstrated with anti-angiogenic monotherapies, and ongoing trials are focused on combination strategies with cytotoxic agents, immunotherapies and other targeted treatments. This article reviews the science behind angiogenesis within the context of gynecologic cancers, the evidence supporting the targeting of these pathways and future directions in clinical trials.
Highlights
It has become increasingly recognized that tumor vascularization and dysregulated angiogenesis are hallmark features of cancer development
Various angiogenic factors are implicated in the process of tumorigenesis, and within the last two decades, advances in drug development have seen the adoption of several anti-angiogenic drugs in routine oncology practice across various tumor types [1]
Lenvatinib is another oral multi-kinase inhibitor that targets VEGF tyrosine kinase receptors (VEGFR)-1 to -3, FGFR14, c-kit, PDGFR and the receptor that is rearranged during transfection (RET) [61]
Summary
It has become increasingly recognized that tumor vascularization and dysregulated angiogenesis are hallmark features of cancer development. Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, has regulatory approval for use across numerous indicators within advanced-stage epithelial ovarian and cervical cancers, mostly in conjunction with chemotherapy [2]. Another angiogenesis inhibitor, lenvatinib, has recently obtained regulatory approval, in combination with pembrozliumab, for subsequent-line treatment of advanced endometrial cancer [2]. In 2000, Hanahan and Weinberg published a framework proposing six hallmarks necessary for cancer growth and development [9] This was updated in 2011 in line with rapid advancements in the scientific understanding of carcinogenic processes reflecting increasing diversity in targeted drug development [10]. Tumor-associated vasculature are disorganized and chaotic, ignoring the standard vascular hierarchy with such abnormal features as precocious capillary sprouting, erratic blood flow, hyperpermeability and abnormal endothelial cell proliferation and behavior [14]
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