Abstract
Epithelial ovarian cancer is a highly lethal disease, which is usually diagnosed at a late stage with extensive metastases in the abdominal cavity. Ovarian cancer either develops from the ovarian surface epithelium (OSE) or from serous intra-epithelial carcinoma (STIC). Primary therapy consists of debulking surgery and platinum based chemotherapy. The success of debulking surgery depends on surgical skills but also on the gene signature of the tumour. Debulking surgery combined with first line platinum based chemotherapy, frequently leads to complete remission. However, most ovarian cancers relapse. Once the disease has relapsed, the interval between subsequent therapies decreases steadily due to rapid progression and therapy resistance. Research on therapy resistance of ovarian cancer is frequently devoted to genetic alterations in cancer cells, leading to drug inactivation, enhanced DNA repair mechanisms and intracellular pathway derangements. However the knowledge of ovarian cancer stem cells (OCSC) and the role they play in the development of cancer and therapy resistance is sparse. In this review current knowledge on the characteristics of OCSCs and the micro environmental mechanisms leading to the development or activation of OCSCs resulting in ovarian cancer is reviewed. Moreover the role of OCSC in both surgical and systemic therapy resistance and the relation with epithelial mesenchymal transformation (EMT) is discussed, as are micro-environmental signals leading to OCSC or EMT activation.
Highlights
Ovarian cancer is the 7th most common cancer in women worldwide and the third most common female cancer after breast and cervix cancer, with an incidence rate of 10–15 per 100,000
Many explanations for this therapy resistance are available: genetic and epigenetic mutations leading to expelling or inactivation of cytotoxic drugs, impaired apoptosis enhanced repair mechanisms and a micro environment leading to inhibition of the immune system all contribute to the poor prognosis of this disease
Endometrioid and clear cell carcinoma would, according to this theory, result from shedding of more proximal tubal tissue or from endometriosis (Fig. 1) (Table 1). Both theories have been merged into one: while the low grade ovarian cancers, such as borderline tumours and low grade serous and endometrioid carcinoma originate from cortical inclusion cysts (CIC) lesions, the high grade serous carcinoma are believed to develop from the secretory cells of the fallopian tube and especially the fimbriae, probably induced by inflammatory stimuli caused by ovulation
Summary
Ovarian cancer is the 7th most common cancer in women worldwide and the third most common female cancer after breast and cervix cancer, with an incidence rate of 10–15 per 100,000. With more lines of therapy multi-drug resistance develops in all patients, leading to increasingly shorter periods of remission or stable disease, resulting in death. Many explanations for this therapy resistance are available: genetic and epigenetic mutations leading to expelling or inactivation of cytotoxic drugs, impaired apoptosis enhanced repair mechanisms and a micro environment leading to inhibition of the immune system all contribute to the poor prognosis of this disease. In this review the hypotheses of the development of ovarian cancer stem cells (OCSC) and the current knowledge of their role in treatment failure as well factors that influence their activity will be discussed
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