Wnt antagonist as therapeutic targets in ovarian cancer.

Abstract

Ovarian cancer is a fatal malignancy in women with a low survival rate that demands new therapeutic paradigms. Cancer cells acquire various exclusive alterations to proliferate, invade, metastasize, and escape cell death, acting independently of growth-inducing or growth-inhibiting signals. The nature of cellular signaling in tumorigenesis is interwoven. Wnt signaling is an evolutionarily conserved signaling cascade that has been shown to regulate ovarian cancer pathogenesis. The molecular mechanism of Wnt signaling underlying the development of ovarian cancer, drug resistance, and relapse is not completely understood. Extracellularly secreted Wnt signaling inhibitors are crucial regulators of ovarian cancer tumorigenesis and malignant properties of cancer stem cells. Wnt inhibitors arbitrated modifications affecting Wnt pathway proteins on the cell membranes, in the cytoplasm, and in the nucleus have been shown to span essential contributions in the initiation, progression, and chemoresistance of ovarian cancer. Although many extrinsic inhibitors developed targeting the downstream components of the Wnt signaling pathway, investigating the molecular mechanisms of endogenous secreted inhibitors might substantiate prognostic or therapeutic biomarkers development. Given the importance of Wnt signaling in ovarian cancer, more systematic studies combined with clinical studies are requisite to probe the precise mechanistic interactions of Wnt antagonists in ovarian cancer. This review outlines the latest progress on the Wnt antagonists and ovarian cancer-specific regulators such as micro-RNAs, small molecules, and drugs regulating these Wnt antagonists in ovarian tumourigenesis.