Cancer stem cells in gynecologic cancer

Abstract

Gynecological cancer is currently the sixth leading cause of death among women. Despite screening campaigns, early diagnosis and vaccination against Human Papilloma Virus, gynecological cancers -mostly ovarian cancer- are often diagnosed at advanced stages. Although the high effectiveness of existing medical treatments, during long term therapy, often seem insufficient to achieve the cure or the disease. This is due to the presence of metastases at the time of diagnosis and to the development of resistance to cytostatic treatments and further recurrences. The discovery and understanding of Cancer Stem Cells (CSCs) leads to an encouraging outlook on the future treatment of these patients. Within the perspective of the CSCs concept model, gynecological CSCs have specific genetic and epigenetic variations that give them capabilities to undergo asymmetric cell divisions, ensuring new generations of CSCs and of more differentiated gynecological cancer cells. As a result of these biological capabilities, CSCs can mediate gynecological cancers occurrence, resistance to treatment and recurrence. In this review we discuss emerging evidences supporting the existence of CSCs in ovarian, endometrial and cervical cancers. Focus is given to recent molecular and genomic advances regarding the characterization of abnormal signaling cascades in these three types of gynecological CSCs. We also discuss the current knowledge on genetic and epigenetic changes in gynecological cancers and CSCs, and how researchers propose that these cellular changes influence CSCs in their control of cancer development and recurrence. We also discuss advances in medical treatment of gynecological cancer using CSCs as a therapeutic target.