Conclusion: Our data suggest that BRCA1-defective in vivo HBCXs express a molecular scenario predictive of high sensitivity to platinum-derived compounds strongly supporting the rationale for prospective tailored clinical trials in hereditary breast cancer.

No abstract

No abstract

PTEN is a tumour suppressor gene, and its loss of function is frequently observed in both heritable and sporadic cancers. It is involved in a great variety of biological processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. A better understanding of PTEN activity and regulation has therefore emerged as a subject of primary interest in cancer research. Gynaecological cancers are variously interested by PTEN deregulation and many perspective in terms of additional prognostic information and new therapeutic approaches can be explored. Here, we present the most significant findings on PTEN in gynaecological cancers (ovarian, endometrial, cervical, vulvar and uterine cancer) focusing on PTEN alterations incidence, biological role and clinical implications.

The advent of Precision Medicine has globally revolutionized the approach of translational research suggesting a patient-centric vision with therapeutic choices driven by the identification of specific predictive biomarkers of response to avoid ineffective therapies and reduce adverse effects. The spread of “multi-omics” analysis and the use of sensors, together with the ability to acquire clinical, behavioral, and environmental information on a large scale, will allow the digitization of the state of health or disease of each person, and the creation of a global health management system capable of generating real-time knowledge and new opportunities for prevention and therapy in the individual person (high-definition medicine). Real world data-based translational applications represent a promising alternative to the traditional evidence-based medicine (EBM) approaches that are based on the use of randomized clinical trials to test the selected hypothesis. Multi-modality data integration is necessary for example in precision oncology where an Avatar interface allows several simulations in order to define the best therapeutic scheme for each cancer patient.

Several genes associated with hereditary ovarian cancer have been discovered as a result of the work done with next generation sequencing. It is estimated that approximately 23% of ovarian carcinomas have a hereditary predisposition. The most common hereditary condition is represented by germline mutations in BRCA1 or BRCA2 genes that account for 20–25% of high grade serous ovarian cancer. A number of other hereditary ovarian cancers are associated with different genes, with a crucial role in the DNA damage response pathway, such as the mismatch repair genes in Lynch syndrome, TP53 in Li-Fraumeni syndrome, STK11 in Peutz-Jeghers syndrome, CHEK2, RAD51, BRIP1, and PALB2. The goal of this manuscript is to summarize the published data regarding the molecular pathways involved in the pathogenesis of non-BRCA related hereditary ovarian cancer and to provide a tool that might be useful in discussing risk assessment, genetic testing, prevention strategies, as well as clinical and therapeutic implications for patients with ovarian cancer.

Background:The NGR-hTNF (asparagine–glycine–arginine–human tumour necrosis factor) is able to promote antitumour immune responses and to improve the intratumoural doxorubicin uptake by selectively damaging tumour blood vessels.Methods:Patients progressing after ⩾1 platinum/taxane-based regimen received NGR-hTNF 0.8 μg m−2 and doxorubicin 60 mg m−2 every 3 weeks. Primary endpoint was a Response Evaluation Criteria in Solid Tumors-defined response rate with a target of more than 6 out of 37 responding patients.Results:A total of 37 patients with platinum-free interval lower than 6 months (PFI<6; n=25), or between 6 and 12 months (PFI=6–12; n=12) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6 per ml (interquartile range, 1.2–2.1). In all, 18 patients (49%) received more than 6 cycles. Febrile neutropaenia was registered in one patient (3%). Among 35 assessable patients, 8 (23% 95% CI 12–39%) had partial response (2 with PFI<6; 6 with PFI=6–12) and 15 (43%) had stable disease (10 with PFI<6; 5 with PFI=6–12). Median progression-free survival (PFS) was 5.0 months for all patients, 3.8 months for patients with PFI<6, and 7.8 months for patients with PFI=6–12. Median overall survival (OS) was 17.0 months. Patients with baseline PBLC higher than the first quartile had improved PFS (P=0.01) and OS (P=0.001).Conclusion:Tolerability and activity of this combination warrant further randomised testing in patients with PFI<6. The role of PBLC as a blood-based biomarker deserves further investigation.

Pemetrexed showed moderate activity against advanced/recurrent cervical cancer that had failed prior chemotherapy.