The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer

Abstract

Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20–30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management.

HDAC6-selective inhibitors enhance anticancer effects of paclitaxel in ovarian cancer cells

“…Ovarian cancer is the second leading cause of female reproductive cancer death. In 2018, ovarian cancer affected approximately 295,414 women worldwide, with a predilection for postmenopausal women (1). Ovarian cancer carries a poor prognosis, with a 5-year survival rate of only 30% and deaths occurring within just 2 years of diagnosis.…”

“…However, despite several clinical trials, regimens containing platinum have not shown improvements for the past 20 years largely due to drug toxicity and resistance. In fact, of the 80% of patients with good initial responses to standard treatments, 70% experience disease recurrence (1). In addition to the problem of drug-resistance, drug-refractory patients exhibit the worst prognosis for treatment (2).…”

Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer, therapeutic treatment options for platinum-resistant ovarian cancer

“…The most prevalent type of ovarian cancer, epithelial ovarian cancer (EOC), is categorized into different histological subtypes: serous (high or low grade), clear cell, endometrioid and mucinous. The classical dualistic classification of EOC into two types (I and II) [3] has been revised and expanded in recent years to take into account numerous molecular and histological studies, which have provided new important insights into EOC [4] , and the updated WHO [5,6] and FIGO classifications [7,8] . Type I tumors, which account for approximately 25% of all EOC, encompass the subtypes low grade serous ovarian cancer (LGSC), endometrioid, mucinous, clear cell, and the rare Brenner tumor subtype.…”

Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia

“…It has been reported that the 5-year survival rate is only 29% in the advanced stage of EOC patients (3). At present, molecular targeted therapy is regarded as one of the most promising therapies for EOC treatment (4). Identifying genes associated with tumorigenesis, proliferation, invasion and migration of EOC has significant implications for EOC clinical treatment and basic research (5).…”