Epithelial Mesenchymal Transition and Cancer Stem Cell-Like Phenotypes Facilitate Chemoresistance in Recurrent Ovarian Cancer

N.      Ahmed; K.      Abubaker; J.      Findlay; M.      Quinn

doi:10.2174/156800910791190175

Abstract

Overcoming intrinsic and acquired chemoresistance is the major challenge in treating ovarian cancer patients. Initially nearly 75% of ovarian cancer patients respond favourably to chemotherapy, but subsequently the majority gain acquired resistance resulting in recurrence, cancer dissemination and death. This review summarizes recent advances in our understanding of the cellular origin and the molecular mechanisms defining the basis of cancer initiation and malignant transformation with respect to epithelial-mesenchymal transition (EMT) of ovarian cancer cells. We discuss the critical role of EMT frequently encountered in different phases of ovarian cancer progression and its involvement in regulating cancer growth, survival, migration, invasion and drug resistance. Using a model ovarian cancer cell line we highlight the relationship between EMT and the ‘migrating cancer stem (MCS) cell-like phenotype’ in response to drug treatment, and relate how these processes can impact on chemoresistance and ultimately recurrence. We propose the molecular targeting of distinct ‘EMT transformed cancer stem-like cells’ and suggest ways that may improve the efficacy of current chemotherapeutic regimens much needed for the management of this disease.

Keywords: Ovarian carcinoma, stem cell markers, EMT, migration, metastasis, differentiation, chemoresistance, recurrence