Abstract
Epithelial ovarian cancer is a fatal disease, with a cure rate of only 30%. Several recent studies have targeted integrins for cancer treatment. Preclinical studies have shown the effectiveness of several integrin inhibitors for blocking cancer progression, especially by blocking angiogenesis. Because the initial critical step in ovarian cancer metastasis is the attachment of cancer cells to the peritoneum or omentum and because clinical trials have provided positive results for anti-angiogenic therapy, therapies targeting integrins may be the most feasible approach for treating cancer. This review summarizes the current understanding of integrin biology in ovarian cancer metastasis and various therapeutic approaches involving integrin inhibitors. However, no integrin inhibitor has shown favorable results thus far. However, conjugates of cytotoxic agents with the triplet sequence arginine-glycine-aspartate (RGD) peptides targeting α5β1-, αvβ3-, and αvβ6-integrins may be promising integrin-targeting therapies for further clinical investigation.
Highlights
Epithelial ovarian cancer (EOC) is one of the most common gynecologic malignancies and the fifth leading cause of cancer-related death in women [1]
Several integrins have been identified as important mediators of ovarian cancer metastasis to the mesothelium [6], suggesting that use of integrin inhibitors could be a new therapeutic strategy to prevent the attachment of cancer cells to the peritoneal cavity
We describe the critical roles of integrins in ovarian carcinoma metastasis and recent progress in targeting integrins for treating several cancers, including ovarian cancer
Summary
Epithelial ovarian cancer (EOC) is one of the most common gynecologic malignancies and the fifth leading cause of cancer-related death in women [1]. EOC is a highly metastatic cancer characterized by widespread peritoneal dissemination and ascites accumulation. It is typically diagnosed in advanced stages [2]. New therapeutic strategies, including molecular targeting therapies, have been recently considered for treating EOC [3]. Ovarian cancer cells float in the peritoneal cavity and attach to secondary sites of implantation, most notably the omentum, which is the most common site of ovarian cancer metastasis [5]. Several integrins have been identified as important mediators of ovarian cancer metastasis to the mesothelium [6], suggesting that use of integrin inhibitors could be a new therapeutic strategy to prevent the attachment of cancer cells to the peritoneal cavity. We describe the critical roles of integrins in ovarian carcinoma metastasis and recent progress in targeting integrins for treating several cancers, including ovarian cancer
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