Oncology and Pharmacogenomics Insights in Polycystic Ovary Syndrome: An Integrative Analysis.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Epidemiological findings revealed that women with PCOS are prone to develop certain cancer types due to their shared metabolic and endocrine abnormalities. However, the mechanism that relates PCOS and oncogenesis has not been addressed. Herein, in this review article the genomic status, transcriptional and protein profiles of 264 strongly PCOS related genes (PRG) were evaluated in endometrial cancer (EC), ovarian cancer (OV) and breast cancer (BC) exploring oncogenic databases. The genomic alterations of PRG were significantly higher when compared with a set of non-diseases genes in all cancer types. PTEN had the highest number of mutations in EC, TP53, in OC, and FSHR, in BC. Based on clinical data, women older than 50 years and Black or African American females carried the highest ratio of genomic alterations among all cancer types. The most altered signaling pathways were p53 in EC and OC, while Fc epsilon RI in BC. After evaluating PRG in normal and cancer tissue, downregulation of the differentially expressed genes was a common feature. Less than 30 proteins were up and downregulated in all cancer contexts. We identified 36 highly altered genes, among them 10 were shared between the three cancer types analyzed, which are involved in the cell proliferation regulation, response to hormone and to endogenous stimulus. Despite limited PCOS pharmacogenomics studies, 10 SNPs are reported to be associated with drug response. All were missense mutations, except for rs8111699, an intronic variant characterized as a regulatory element and presumably binding site for transcription factors. In conclusion, in silico analysis revealed key genes that might participate in PCOS and oncogenesis, which could aid in early cancer diagnosis. Pharmacogenomics efforts have implicated SNPs in drug response, yet still remain to be found.

Neoadjuvant chemotherapy and interval debulking surgery for advanced ovarian cancer, an alternative with multiple advantages.

Ovarian cancer, which is mostly diagnosed in advanced stages, is a disease with high mortality among women. Until now, no screening strategies have been accepted and are currently under study because although they help in the diagnosis at early stages, they do not increase survival. The gold standard treatment for advanced ovarian cancer is based on primary debulking surgery (PDS) follow by adjuvant chemotherapy (ACT) with paclitaxel and carboplatin. Recently, treatment alternatives have been proposed: neoadjuvant chemotherapy (NAC) with interval debulking surgery (IDS). This approach has been controversial due to the lack of clinical data on the validity as a safe and successful procedure and because of the high morbidity and mortality associated to this disease. The most important prognostic factor for survival is no residual tumor after surgery; despite of this, numerous tumors do not fulfill the criteria for performing a PDS and associated morbidity is unacceptable high. Based on selected clinical features, NAC-IDS could be a reasonable alternative to those patients with reversible contraindications to primary surgery with the only objective of improving survival and quality of life (QOL). Although, several papers have reported that NAC could induce ACT resistance, neither randomized controlled trials nor meta-analyses have demonstrated this fact. The true is that more advantages have been reported: NAC groups trend toward higher QOL and lower rates of postoperative adverse events. This has been confirmed by two randomized clinical trials, but further studies are needed to support the role of NAC. Meanwhile, patients should receive the best opportunities and the best option for treating this type of cancer.