Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.

Ovarian cancer is a leading cause of death among gynecologic malignancies. This disappointing prognosis is closely related to intrinsic or acquired resistance to conventional platinum-based chemotherapy, which can affect a third of patients. As such, investigating relevant molecular targets is crucial in the fight against this disease. So far, many mutations involved in ovarian cancer pathogenesis have been identified. Among them, a few pathways were implicated. One such pathway is the P13K/AKT/mTOR with abnormalities found in many cases. This pathway is considered to have an instrumental role in proliferation, migration, invasion and, more recently, in chemotherapy resistance. Many miRNAs have been found to influence P13K/AKT/mTOR pathway with different potential role in tumor genesis and ovarian cancer behaviour. In particular, their biological function was recently investigated as regards chemoresistance, therefore, leading to the identification of potential specific indirect biomarker of platinum sensitivity in ovarian cancer.

Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.

It has been widely demonstrated that endocrine disruptors play a central role in various physiopathological processes of human health. In the literature, various carcinogenic processes have been associated with endocrine disruptors. A review of the molecular mechanisms underlying the interaction between endocrine disruptors and the endometrial cancer has been poorly developed. A systematic review was performed using PubMed®/MEDLINE. A total of 25 in vivo and in vitro works were selected. Numerous endocrine disruptors were analyzed. The most relevant results showed how Bisphenol A (BPA) interacts with the carcinogenesis process on several levels. It has been demonstrated how BPA can interact with hormonal receptors and with different transcription proliferative and antiproliferative factors. Furthermore, the effect of Polycyclic aromatic hydrocarbons on Aryl hydrocarbon receptors was investigated, and the role of flame retardants in promoting proliferation and metastasis was confirmed. The results obtained demonstrate how the mechanisms of action of endocrine disruptors are manifold in the pathophysiology of endometrial cancer, acting on different levels of the cancerogenesis process.

Several available studies have already analyzed the systemic effects of endocrine-disrupting chemicals (EDCs) on fertile woman and neonatal outcomes, but little is still known in humans about the precise mechanisms of interference of these compounds with the endometrial receptivity. There is consistent evidence that continuous and prolonged exposure to EDCs is a risk factor for reduced fertility and fecundity in women. Preliminary studies on mammalian models provide robust evidence about this issue and could help gynecologists worldwide to prevent long term injury caused by EDCs on human fertility. In this systematic review, we aimed to systematically summarize all available data about EDC effects on blastocyst endometrial implantation. We performed a systematic review using PubMed®/MEDLINE® to summarize all in vivo studies, carried out on mice models, analyzing the molecular consequences of the prolonged exposure of EDC on the implantation process. 34 studies carried out on mouse models were included. Primary effects of EDC were a reduction of the number of implantation sites and pregnancy rates, particularly after BPA and phthalate exposure. Furthermore, the endometrial expression of estrogen (ER) and progesterone receptors (PR), as well as their activation pathways, is compromised after EDC exposure. Finally, the expression of the primary endometrial markers of receptivity (such as MUC1, HOXA10, Inn and E-cadherin) after EDC contact was analyzed. In conclusion EDC deeply affect blastocyst implantation in mouse model. Several players of the implantation mechanism are strongly influenced by the exposure to different categories of EDC.