Collaboration of Epithelial Mesenchymal Transition and Cancer Stem Cells: Sinister Routes for Chemoresistant Recurrent Ovarian Cancer
Pp. 118-155 (38)
N. Ahmed, K. Abubaker, E. Chan, G. Kannourakis and J.K. Findlay
Overcoming intrinsic and acquired chemoresistance is the major challenge in
treating ovarian cancer patients. Initially nearly 75% of ovarian cancer patients respond
favorably to chemotherapy, but subsequently the majority gain acquired resistance
resulting in recurrence, cancer dissemination and death. This chapter 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 model ovarian cancer cell lines we highlight the
relationship between EMT and the ‘cancer stem cell (CSC)-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 CSC-like cells’ and suggest ways that may improve the efficacy of current
chemotherapeutic regimens much needed for the management of this disease.
Chemoresistance, Differentiation, EMT, Metastasis, Migration, Ovarian carcinoma, Recurrence, Stem cell markers.
Fiona Elsey Cancer Research Institute, 106-110 Lydiard Street South, Central Park, Ballarat, Vic 3363, Australia.