Elena Giudice

Genome tumor profiling in endometrial cancer and clinical relevance in endometrial cancer management: a retrospective single-center experience

Next-generation sequencing (NGS) analysis has become an essential tool for endometrial carcinoma management. Moreover, molecular-driven therapies play an increasingly remarkable role in the era of precision oncology. This study aims to determine the clinical relevance of NGS testing in endometrial carcinoma management by analyzing the clinical benefit of NGS-driven targeted therapies. A single-center retrospective study was conducted on 25 endometrial carcinoma patients who underwent Foundation Medicine CDx assay at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS (Rome, Italy). Tumor samples were analyzed by Foundation One CDx. A descriptive analysis of tumor genome profiles was performed. Assessment of clinical benefit according to RECIST 1.1 criteria was analyzed for patients who received a tailored treatment according to actionable targets identified by NGS testing. Out of 25 endometrial carcinoma patients, 11 received targeted therapy. One patient was excluded from the clinical benefit assessment because of COVID-19-related death 1 month after starting the treatment. Eight of the remaining 10 patients benefited from targeted therapies, with an overall clinical benefit rate of 80%. A targeted agent belonging to the PI3K pathway was given to seven patients, with evidence of three partial responses (42.9%), three stable diseases (42.9%), and one progressive disease (14.2%) according to RECIST 1.1 criteria. One complete response (33.3%), one stable disease (33.3%), and one progressive disease (33.3%) were observed in the three patients treated with poly(ADP-ribose) polymerase (PARP) inhibitors according to their homologous recombination deficiency (HRD) status. This study highlights the importance of characterizing the mutation profile of patient tumors through NGS. Our findings suggest a clinical benefit of using NGS-driven targeted therapies in endometrial carcinoma patients. However, this personalized approach could benefit the health system in terms of cost-effectiveness by reducing the costs of inappropriate, ineffective, and often expensive treatments.

Recent progress in the use of pharmacotherapy for endometrial cancer

Endometrial cancer (EC) is the most common gynecological cancer in developed countries. The ESGO/ESTRO/ESP updated evidence-based guidelines in 2020, introducing molecular classification to guide EC treatment. The genomic-based approach has identified four prognostic subgroups of EC. Each of these may benefit from a tailored treatment depending on the molecular profile, the histotype, and stage of disease for the adjuvant and the metastatic/recurrent setting. Several clinical trials are now ongoing to identify the best treatment according to the molecular profile of EC. This review analyzes tailored treatment for EC according to the molecular profile, both in the adjuvant and in the metastatic/recurrent setting. The authors review the results of clinical studies and highlight ongoing trials. Several new agents are under evaluation in order to personalize EC treatment according to specific molecular profiles in the adjuvant, advanced, and recurrent settings. Clinical trials investigating the impact of molecular classification have yielded encouraging results. EC can no longer be considered a single tumor entity susceptible to a single treatment modality but rather be split into four distinct types, requiring tailored treatments.

Management of stage III and IVa uterine cancer

The prognosis of patients with advanced endometrial cancer is poor with limited therapeutic options. Nevertheless, the integration of molecular features in the clinico-pathological classification of endometrial cancer has significantly refined prognostic risk groups, representing a major breakthrough not only in the management of the disease but also in treatment perspectives. New therapeutic compounds such as target therapies, immunotherapy, and hormonal therapies have emerged for this clinical setting. Furthermore, molecular-driven clinical trials may improve significantly the efficacy of new treatments selecting those patients who are highly likely to respond. This review aims at describing the state of the art of advanced stage III-IVa endometrial cancer management, providing also the most interesting clinical perspectives.

Survival outcomes in patients with BRCA mutated, variant of unknown significance, and wild type ovarian cancer treated with PARP inhibitors

Correlation between Patients with ovarian cancer whose somatic Of 67 patients identified, 20 (29.9%), 24 (35.8%), and 23 (34.3%) had BRCA variant of unknown significance, mutated, and wild type, respectively. Patients received PARPi as maintenance treatment at the time of the first relapse after a complete response or partial response to platinum-based chemotherapy without differences in the previous platinum-free interval among the analyzed groups. The median progression-free survival of patients with Our study suggests that carriers of BRCA variant of unknown significance have survival outcomes comparable to patients with

Gut microbiota and its influence on ovarian cancer carcinogenesis, anticancer therapy and surgical treatment: A literature review

Ovarian cancer (OC) is the most lethal gynecological malignancy and very little is known about the underlying tumorigenesis mechanisms. For other tumors, like colorectal cancer, a relationship between several opportunistic pathogens and cancer development and progression has been proven. Recent researches also underline a possible correlation between gut microbiota dysbiosis and cancer treatment efficacy and adverse effects. Several studies have also demonstrated a link between abdominal surgery and gut microbiota modifications. In this paper, we aim to review the available evidences of this issue in OC to understand if there is a relationship between gut microbiota modifications and efficacy and adverse effects of cancer therapies, either surgical and medical treatments. Well-designed clinical studies, with a robust translational component, are required to better understand the modulation of gut microbiota during OC treatment. The microbiota/microbiome composition analysis, in the near future, could represent a novel instrument to personalize anticancer therapies.

The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial

Abstract The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR). Secondary outcomes were safety and progression-free survival (PFS). 49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6). Among the 39 RECISTv1.1-evaluable patients, ORR was 33.3% in cohort 5 and 28.6% in cohort 6. Primary endpoint was not evaluable due to early stop of the trial. The median PFS was 4 months in cohort 5 and 6 months in cohort 6. Toxicity was manageable. Translational research was an exploratory endpoint. Potential biomarkers were investigated using pre-treatment fresh biopsies and serial blood samples. Transcriptomic analysis revealed high levels of DNA replication-related genes (POLA1, POLE, GINS3) associated with lack of clinical benefit [defined post-hoc as PFS < 6 months]. Subsequent preclinical experiments demonstrated significant cytotoxicity of POLA1 silencing in combination with CHK1i in platinum-resistant HGSOC cell line models. Therefore, POLA1 expression may be predictive for CHK1i resistance, and the concurrent POLA1 inhibition may improve the efficacy of CHK1i monotherapy in this hard-to-treat population, deserving further investigation.

Neoadjuvant chemotherapy followed by interval surgery versus primary debulking surgery in FIGO stage III-IV epithelial ovarian cancer: A systematic review and meta-analysis.

To compare survival and perioperative outcomes of Primary debulking surgery (PDS) versus neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) in newly diagnosed FIGO stage III-IV ovarian cancer. Primary outcomes were overall survival (OS) and progression-free survival (PFS). MEDLINE, Embase, CENTRAL, Web of Science, Scopus, Cochrane Library, major conference proceedings (inception to July 13, 2025) STUDY SELECTION: Phase-III randomized trials comparing survival outcomes between PDS and NACT-IDS, enrolling adults with newly diagnosed stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. Following PRISMA, two reviewers independently screened, extracted and assessed risk-of-bias (RoB 1). Random-effects meta-analysis estimated pooled hazard ratios (HRs) for OS/PFS and risk ratios (RRs) for binary endpoints. Heterogeneity was quantified with the I² statistic. PROSPERO (CRD420251056445). Five RCTs (n = 2380 women), including one conference-only report, met criteria. NACT-IDS yielded no difference in OS (HR 1.00; 95 % CI 0.90-1.12; I² = 16 %) and PFS (HR 1.03; 95 % CI 0.92-1.16; I² = 39 %) versus PDS. Grade ≥ 3 perioperative complications were significantly less frequent with NACT-IDS (RR 0.43; 95 % CI 0.25-0.74; I² = 75 %) while CC-0 rates were higher (RR 2.02; 95 % CI 1.26-3.24; I² = 94 %). In FIGO stage III-IV, NACT-IDS achieves survival endpoints similar to PDS, while increasing the likelihood of complete macroscopic resection and reducing severe perioperative morbidity. Upfront surgery in advanced ovarian cancer management should likely be reserved for patients with feasible complete resection and presumed low morbidity.