Poly (ADP-ribose) polymerase (PARP) as target for the treatment of epithelial ovarian cancer: what to know.

INTRODUCTION: Poly (ADP-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings of epithelial ovarian cancers (EOCs) with BRCA 1-2 gene mutation. PARP inhibitors are the first example of drugs targeting the loss of a gene suppressor: they block base-excision repair in the cancer cells, which have lost homologous recombination due to BRCA-mutation, resulting in loss of DNA repair and cell death, also known as synthetic lethality. AREAS COVERED: This article provides an overview of PARP inhibitors in OC treatment and also an extensive section on the combined strategies of PARP inhibitors, including approved as well as currently investigated drugs. It also offers a section on the use of predictive biomarkers for PARP inhibitors treatment. Ongoing trials, including novel combinations, are discussed. EXPERT OPINION: In recent years, there is increasing evidence that PARP inhibitor therapy can have life-long percussion in the treatment of EOC, even if some questions have to be solved yet, such as its use in combination therapy, the possibility to retreat with a PARP inhibitor, and finally how to overcome a resistance mechanism to this therapy. In this way, PARP inhibitors can obtain an important role in making a personalized therapeutic program in the case of first-line, neoadjuvant, platinum-sensitive, and resistant high-grade serous OC treatment.

Microbiome and PCOS: State-of-Art and Future Aspects.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

Role of biomarkers for early detection of ovarian cancer recurrence.

Ovarian cancer is frequently diagnosed at an advanced stage and a fraction of these patients fail to respond to primary therapy and relapses in 70% of cases. On account of the high recurrence probability and the poor outcomes after recurrence, there is an urgent need to predict progression as early as possible and thus found the strategies to detect and prevent a recurrence. Considering that biomarkers have contributed to the management of ovarian cancer by distinguishing benign and malignant pelvic masses and monitoring response to treatment, in this review, we aim to discuss the latest evidence reported in the literature about the use of biomarkers to detect OC recurrence. In detail, we summarized all the evidence of the most quoted biomarkers like HE4, osteopontin, mesothelin (MSLN), Folate receptor α (FOLR1), paraneoplastic antigens, miRNA, cancer stem cells (CSCs) and a combination of them to evaluate their role as prognostic biomarkers for ovarian cancer recurrence.

The Burden of Endometriosis on Women's Lifespan: A Narrative Overview on Quality of Life and Psychosocial Wellbeing.

Endometriosis is a chronic, inflammatory disease affecting more than 170 million women worldwide and up to 10% of women of reproductive age. As a consequence of inflammatory reaction and infiltration of anatomic structures, endometriosis can cause "pain symptoms" including dysmenorrhea, dyspareunia, dyschezia, dysuria, and chronic pelvic pain. In this review, we summarized the impact of endometriosis on quality of life in all its aspects including sexual life, work, and social relationships. The data research was conducted using web-based search engines and/or various electronic research databases querying for all articles related to endometriosis and quality of life from the inception of the database up to February 2020. Endometriosis has not only physical but also psychological effects, causing depression, anxiety, and compromising social relationships. Furthermore, endometriosis negatively impacts sexual life and social relationships. At last, the economic burden of endometriosis should not be underestimated, both individually and for the community, as this pathology leads to a loss of productivity at work and large use of health resources. Thus, endometriosis-related symptoms control women's lives compromising the quality of life in all aspects. In this review, we summarized the impact of endometriosis on various aspects of women's lives.

Advances in therapeutic vaccines for treating human papillomavirus-related cervical intraepithelial neoplasia.

AIM: Human papillomavirus (HPV) is the etiologic agent of the majority of cervical intraepithelial lesions (CIN) and cervical cancers. While prophylactic HPV vaccines prevent infections from the main high-risk HPV types associated with cervical cancer, alternative nonsurgical and nonablative therapeutics to treat HPV infection and preinvasive HPV diseases have been experimentally investigated. Therapeutic vaccines are an emerging investigational strategy. This review aims to introduce the results of the main clinical trials on the use of therapeutic vaccines for treating HPV infection and -related CIN, reporting the ongoing studies on this field. METHODS: Data research was conducted using MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library querying for all articles related to therapeutic vaccines for the treatment of HPV-related CIN. Selection criteria included randomized clinical trials, nonrandomized controlled studies and review articles. RESULTS: Preliminary data are available on the evaluation of therapeutic vaccines for treating cervical HPV infections and CIN. Despite having in vitro demonstrated to obtain humoral and cytotoxic responses, therapeutic vaccines have not yet clinically demonstrated consistent success; moreover, each class of therapeutic vaccines has advantages and limitations. Early clinical data are available in the literature for these compounds, except for MVA E2, which reached the phase III clinical trial status, obtaining positive clinical outcomes. CONCLUSION: Despite promising results, to date many obstacles are still present before hypothesize an introduction in the clinical practice within the next years. Further studies will draw a definitive conclusion on the role of therapeutic vaccines in this setting.