An Overview of Ovarian Cancer: The Role of Cancer Stem Cells in Chemoresistance and a Precision Medicine Approach Targeting the Wnt Pathway with the Antagonist sFRP4

SIMPLE SUMMARY: Ovarian cancer is one of the deadliest cancers in women and is unfortunately detected only in its later stages, by which time it will have metastasized to different organs. One of the major determinants of the rapid proliferation and spread of cancer is the presence of cancer stem cells (CSCs) within tumors. In this review, we discuss the emerging markers of ovarian cancer with respect to CSCs and circulating tumor cells. Cancer stem cell population is regulated by the Wnt signaling pathway, which is described in detail. This is relevant to comprehend the significance of Wnt in regulating the stem cell-like properties of cancer. Cancer stem cells are also responsible for enhancing chemoresistant properties and metastatic potential. Therefore, for a successful treatment regime, it is important to factor in drugs that are specific to CSCs. By targeting the promoters of CSCs, such as the Wnt signaling pathway, it is possible to suppress these cells specifically. Herein, we describe an inhibitor of Wnt, secreted frizzled related protein 4, which could be used to successfully destroy the cancer stem cells of ovarian cancer. ABSTRACT: Ovarian cancer is one of the most prevalent gynecological cancers, having a relatively high fatality rate with a low five-year chance of survival when detected in late stages. The early detection, treatment and prevention of metastasis is pertinent and a pressing research priority as many patients are diagnosed only in stage three of ovarian cancer. Despite surgical interventions, targeted immunotherapy and adjuvant chemotherapy, relapses are significantly higher than other cancers, suggesting the dire need to identify the root cause of metastasis and relapse and present more precise therapeutic options. In this review, we first describe types of ovarian cancers, the existing markers and treatment modalities. As ovarian cancer is driven and sustained by an elusive and highly chemoresistant population of cancer stem cells (CSCs), their role and the associated signature markers are exhaustively discussed. Non-invasive diagnostic markers, which can be identified early in the disease using circulating tumor cells (CTCs), are also described. The mechanism of the self-renewal, chemoresistance and metastasis of ovarian CSCs is regulated by the Wnt signaling pathway. Thus, its role in ovarian cancer in promoting stemness and metastasis is delineated. Based on our findings, we propose a novel strategy of Wnt inhibition using a well-known Wnt antagonist, secreted frizzled related protein 4 (sFRP4), wherein short micropeptides derived from the whole protein can be used as powerful inhibitors. The latest approaches to early diagnosis and novel treatment strategies emphasized in this review will help design precision medicine approaches for an effective capture and destruction of highly aggressive ovarian cancer.