Abstract
Ovarian cancer (OC) is the foremost lethal gynaecologic malignancy and among the top five deadliest cancers in women. Current treatment comprises a combination therapy of surgery, platinum-based chemotherapy and anti-vascular endothelial growth factor (VEGF) antibodies. However, patients typically experience a disease relapse within two years. Recurrent OC is incurable and resistance to platins and anti-VEGF treatment is a major determinant of prognosis. Understanding the molecular mechanisms that contribute to tumour metastasis and chemoresistance are essential to improve patient outcome and especially survival. In a current 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.
Highlights
The frontline therapy of ovarian cancer (OC) consists of surgery and platinum-based chemotherapy [1]
Response rates and complete responses after first-line treatment of advanced disease are >80% and 40–60%, respectively, most patients will relapse with a median progression-free survival (PFS) of 18 months [3]
Primary “platinumrefractory” OC patients are quite uncommon and usually seen with non-serous ovarian cancers such as clear cell or mucinous cancers rather than the more common high grade serous ovarian cancer (HGSOC)
Summary
The frontline therapy of ovarian cancer (OC) consists of surgery and platinum-based chemotherapy (usually carboplatin area under the curve [AUC] 5–6 and paclitaxel 175 mg/m2 every 3 weeks for six cycles as demonstrated in the GOG-158 study) [1]. Response rates and complete responses after first-line treatment of advanced disease are >80% and 40–60%, respectively, most patients will relapse with a median progression-free survival (PFS) of 18 months [3]. Most of “platinum-sensitive” patients will respond to further platinum-based chemotherapy with response rates ranging from 30 to 90% [5]. “platinum-resistant” patients typically have low response rates (15%) to subsequent chemotherapy and the outcome of these patients is poor with a median survival not exceeding 12 months [5]. Combining bevacizumab with chemotherapy in platinum-resistant OC improved PFS (HR 0.48; 95% CI, 0.38 to 0.60; P < 0.001) [10]
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