Epithelial ovarian cancer is typically diagnosed at an advanced stage. Current state-of-the-art surgery and chemotherapy result in the high incidence of complete remissions; however, the recurrence rate is also high. For most patients, the disease eventually becomes a continuum of symptom-free periods and recurrence episodes. Different targeted treatment approaches and biological drugs, currently under development, bring the promise of turning ovarian cancer into a manageable chronic disease. In this review, we discuss the current standard in the therapy for ovarian cancer, major recent studies on the new variants of conventional therapies, and new therapeutic approaches, recently approved and/or in clinical trials. The latter include anti-angiogenic therapies, polyADP-ribose polymerase (PARP) inhibitors, inhibitors of growth factor signaling, or folate receptor inhibitors, as well as several immunotherapeutic approaches. We also discuss cost-effectiveness of some novel therapies and the issue of better selection of patients for personalized treatment.

did not derive from high-versus low-grade serous carcinomas and were unrelated to histological (ovarian vs. fallopian) origin. Interestingly, there was considerable overlap between identified prognostic signature and a recently described invasion-associated signature related to stromal desmoplastic reaction. Several genes from this signature were validated by quantitative PCR; two of them-DSPG3 and LOX-were validated both in the initial and independent sets of samples and were significantly associated with OS and disease-free survival. Conclusions We distinguished two molecular subgroups of serous ovarian cancers characterized by distinct OS. Among differentially expressed genes, some may potentially be used as prognostic markers. In our opinion, unsupervised methods of microarray data analysis are more effective than supervised methods in identifying intrinsic, biologically sound sources of variability. Moreover, as histological type of the tumor is the greatest source of variability in ovarian cancer and may interfere with analyses of other features, it seems reasonable to use histologically homogeneous groups of tumors in microarray experiments.

High-grade serous ovarian carcinoma (HGSOC) is the most frequent histological type of ovarian cancer and the one with worst prognosis. Unfortunately, the majority of established ovarian cancer cell lines which are used in the research have unclear histological origin and probably do not represent HGSOC. Thus, new and reliable models of HGSOC are needed. Ascitic fluid from a patient with recurrent HGSOC was used to establish a stable cancer cell line. Cells were characterized by cytogenetic karyotyping and short tandem repeat (STR) profiling. New generation sequencing was applied to test for hot-spot mutations in 50 cancer-associated genes and fluorescence in situ hybridization (FISH) analysis was used to check for TP53 status. Cells were analyzed for expression of several marker genes/proteins by reverse-transcription polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting (FACS), and immunocytochemistry (ICC). Functional tests were performed to compare OVPA8 cells with five commercially available and frequently used ovarian cancer cell lines: SKOV3, A2780, OVCAR3, ES2, and OAW42. Our newly-established OVPA8 cell line shows morphologic and genetic features consistent with HGSOC, such as epithelial morphology, multiple chromosomal aberrations, TP53 mutation, BRCA1 mutation, and loss of one copy of BRCA2. The OVPA8 line has a stable STR profile. Cells are positive for EpCAM, CK19, and CD44; they have relatively low plating efficiency/ability to form spheroids, a low migration rate, and intermediate invasiveness in matrigel, as compared to other ovarian cancer lines. OVPA8 is sensitive to paclitaxel and resistant to cisplatin. We also tested two FGFR inhibitors; OVPA8 cells were resistant to AZD4547 (AstraZeneca, London, UK), but sensitive to the new inhibitor CPL304-110-01 (Celon Pharma, Łomianki/Kiełpin, Poland). We have established and characterized a novel cell line, OVPA8, which can be a valuable preclinical model for studies on high-grade serous ovarian cancer.

An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response.

Nowadays, targeted therapy plays a growing role in oncological treatment. In ovarian cancer, particularly promising results are achieved with poly (ADP-ribose) polymerase (PARP) inhibitors. Recent clinical trials have shown that PARP inhibitors can result in significantly longer progression-free survival. These results encourage the search for other targeted therapies and bring hope that ovarian cancer can soon become a manageable chronic disease. The main problem in ovarian cancer research is the heterogeneity of this disease. Recent studies have shown that different histological types of ovarian cancer can originate from distinct tissues. According to the recent knowledge, "ovarian cancer" is an artificial term for distinct invasive malignancies localised within the pelvis. Genetic and immunophenotype analyses have shown that high-grade serous ovarian cancer, the most frequent histological type and the one with the worst prognosis, originates mainly from fallopian tube epithelium, while endometrioid and clear-cell cancers originate from the endometrium. For these reasons, in basic and preclinical studies on ovarian cancer, one has to carefully choose a well-defined model system, corresponding to the histological type of interest. In this article, we discuss ovarian cancer cell lines most frequently used in in vitro studies. Our aim is to indicate the advantages and disadvantages of different models, encompassing primary and established cell cultures, two-and three-dimensional models, etc. In particular, we would like to alert researchers to the fact that the most popular cell lines SKOV3 and A2780 do not represent a suitable model for studies on high-grade serous ovarian cancer.