Resistance to chemotherapy and anti-angiogenic therapy in ovarian cancer

Ovarian cancer (OC) is the foremost lethal gynaecologic malignancy and among the top five deadliest cancers in women. Current treatment comprises acombination therapy of surgery, platinum-based chemotherapy and anti-vascular endothelial growth factor (VEGF) antibodies. However, patients typically experience adisease relapse within two years. Recurrent OC is incurable and resistance to platins and anti-VEGF treatment is amajor determinant of prognosis. Understanding the molecular mechanisms that contribute to tumour metastasis and chemoresistance are essential to improve patient outcome and especially survival. In acurrent OC model, tumour metastasis and chemoresistance critically depend on the biology of cancer stem cells (CSCs). Recent studies also suggest that intratumour heterogeneity is the main cause of treatment failure due to chemoresistance. Furthermore, the proinflammatory tumour microenvironment seems to contribute to metastasis and chemoresistance. Despite an improved understanding of the complex interplay between classical mechanisms of drug inactivation or efflux, clonal selection and the tumour microenvironment, mechanisms of resistance in human OC are poorly understood. This review summarises current concepts in the treatment of OC, mechanisms of resistance to chemotherapy and angiogenic inhibitors and approaches to overcome drug resistance.