Abstract
Epithelial ovarian cancer (EOC) constitutes 90% of ovarian cancers (OC) and is the eighth most common cause of cancer-related death in women. The cancer histologically and genetically is very complex having a high degree of tumour heterogeneity. The pathogenic variability in OC causes significant impediments in effectively treating patients, resulting in a dismal prognosis. Disease progression is predominantly influenced by the peritoneal tumour microenvironment rather than properties of the tumor and is the major contributor to prognosis. Standard treatment of OC patients consists of debulking surgery, followed by chemotherapy, which in most cases end in recurrent chemoresistant disease. This review discusses the different origins of high-grade serous ovarian cancer (HGSOC), the major sub-type of EOC. Tumour heterogeneity, genetic/epigenetic changes, and cancer stem cells (CSC) in facilitating HGSOC progression and their contribution in the circumvention of therapy treatments are included. Several new treatment strategies are discussed including our preliminary proof of concept study describing the role of mitochondria-associated granulocyte macrophage colony-stimulating factor signaling protein (Magmas) in HGSOC and its unique potential role in chemotherapy-resistant disease.
Highlights
Most ovarian cancers (OC) are high grade malignancies involving one or both ovaries, with substantial metastatic potential [1,2]
We demonstrate that macrophage colony-stimulating factor signaling protein (Magmas) mRNA expression is enhanced in ovarian cancer cell lines in response to chemotherapy treatments, and that enhanced Magmas expression coincides with enhancement in the mRNA expression of drug-resistant gene excision repair complementation complex protein 1 (ERCC1) and embryonic stem cell marker Oct4 (Figure 3)
high-grade serous ovarian cancer (HGSOC) is a deadliest form of cancer due to its widespread peritoneal dissemination at diagnosis and frequent episodes of recurrences, which results in peritoneal organ failure leading to patient’s morbidity
Summary
Most ovarian cancers (OC) are high grade malignancies involving one or both ovaries, with substantial metastatic potential [1,2]. Clinical studies have confirmed that the majority of women who undertook salpingo-oophorectomy due to the presence of BRCA1, 2 mutations had STICs in the fallopian tube Most of these carcinomas were present in the fimbria (finger-like projections at the end of the fallopian tube) of the fallopian tube, suggesting that the fimbria may be the origin of HGSOC [13,21,22]. These tumours follow a stepwise progression from a benign precursor lesion to a malignant state [32] They have accelerated mitotic index and an active DNA damage repair mechanisms (DDR) with effective ‘p53 signature’ [13,31]. Genetic studies have demonstrated type-1 tumours to group independently of type-2 tumours, implicating that these two groups have a different genetic basis [24]
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