Over 50% of breast tumors harbor alterations in one or more genes of the phosphatidylinositol 3-kinase (PI3K) pathway including PIK3CA mutations (31%), PTEN loss (34%), PTEN mutations (5%) and AKT1 mutations (3%). While PI3K and mTOR inhibitors are already approved in advanced breast cancer, AKT inhibitors have been recently developed as a new therapeutic approach. Capivasertib (AZD5363) is a novel, selective ATP-competitive pan-AKT kinase inhibitor that exerts similar activity against the three AKT isoforms, AKT1, AKT2, and AKT3. Preclinical studies demonstrated efficacy of capivasertib in breast cancer cell lines as a single agent or in combination with anti-HER2 agents and endocrine treatment, especially in tumors with PIK3CA or MTOR alterations. Phase I/II studies demonstrated greater efficacy when capivasertib was co-administered with paclitaxel, fulvestrant in hormone receptor (HR)-positive, HER2-negative breast cancer or olaparib. The recommended phase II dose of capivasertib as monotherapy was 480 mg bid on a 4-days-on, 3-days-off dosing schedule. Toxicity profile proved to be manageable with hyperglycemia (20–24%), diarrhea (14–17%) and maculopapular rash (11–16%) being the most common grade ≥3 adverse events. Ongoing Phase III trials of capivasertib in combination with fulvestrant (CAPItello-291), CDK4/6 inhibitor palbociclib (CAPItello-292) and paclitaxel (CAPItello- 290) will better clarify the therapeutic role of capivasertib in breast cancer.

Uterine sarcomas consist a heterogeneous group of mesenchymal gynecological malignancies with unclear therapeutic recommendations and unspecific but poor prognosis, since they usually metastasize and tend to recur very often, even in early stages. We retrospectively analyzed all female patients with uterine sarcomas treated in our institution over the last 17 years. Clinico-pathological data, treatments and outcomes were recorded. Kaplan-Meier curves were plotted and time-to-event analyses were estimated using Cox regression. Data were retrieved from 61 women with a median age of 53 (range: 27–78) years, at diagnosis. Fifty-one patients were diagnosed with leiomyosarcoma (LMS), 3 with high grade endometrial stromal sarcoma (ESS), 5 with undifferentiated uterine sarcoma (UUS), 1 with Ewing sarcoma (ES) and 1 with Rhabdomyosarcoma (RS). 24 cases had stage I, 7 stage II, 14 stage III and 16 stage IV disease. Median disease-free survival (DFS) in adjuvant approach was 18.83 months, and median overall survival (OS) 31.07 months. High mitotic count (> 15 mitoses) was significantly associated with worse OS (P < 0.001) and worse DFS (P = 0.028). Mitotic count appears to be independent prognostic factor while further insights are needed to improve adjuvant and palliative treatment of uterine sarcomas.

Objective: Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, limited data exist for cancer patients under systemic therapy. Methods: In this cohort, we prospectively enrolled cancer patients treated with PARPi as well as healthy volunteers in order to study the kinetics of anti-SARS-CoV-2 antibodies (NAbs) after COVID-19 vaccination. Baseline demographics, co-morbidities, and NAb levels were compared between the two groups. Results: The results of the cohort of 36 patients receiving PARP inhibitors are presented here. Despite no new safety issues being noticed, their levels of SARS-CoV-2 neutralizing antibodies were significantly lower in comparison to matched healthy volunteers up to day 30 after the second dose. Conclusions: These results suggest that maintaining precautions against COVID-19 is essential for cancer patients and should be taken into consideration for the patients under treatment, while further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.

Considering that COVID-19 could adversely affect cancer patients, several countries have prioritized this highly susceptible population for vaccination. Thus, rapidly generating evidence on the efficacy of SARS-CoV-2 vaccination in the subset of patients with cancer under active therapy is of paramount importance. From this perspective, we launched the present prospective observational study to comprehensively address the longitudinal dynamics of immunogenicity of both messenger RNA (mRNA) and viral vector-based vaccines in 85 patients treated with immune checkpoint inhibitors (ICIs) for a broad range of solid tumors. Despite the relatively poor humoral responses following the priming vaccine inoculum, the seroconversion rates significantly increased after the second dose. Waning vaccine-based immunity was observed over the following six months, yet the administration of a third booster dose remarkably optimized antibody responses. Larger cohort studies providing real-world data with regard to vaccines effectiveness and durability of their protection among cancer patients receiving immunotherapy are an increasing priority.

Background: High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline BRCA1/2 mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the BRCA1/2 genes affects the clinical outcome of HGSOC patients. Methods: A total of 51 women with BRCA1 or BRCA2 mutated ovarian cancer were identified. Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: In our study cohort, 35 patients were carriers of germline mutations in BRCA1 and 16 in BRCA2. The median PFS time following completion of the primary therapy was 23.8 months (95% CI 20.1–27.5) and the median OS was 92.9 months (95% CI 69.8–116.1) in all BRCA carriers. After multivariate analysis, no significant association among the location or type of BRCA1/2 mutation with PFS or OS was identified. Notably, significant differences in PFS between carriers of identical mutations in the same BRCA gene were detected. Conclusions: Among HGSOC patients, BRCA1/2 carriers with mutations in different locations of the genes show no significant difference in survival outcomes, in terms of PFS and OS, suggesting the potential effect of other genetic abnormalities and co-contributing risk factors.

Uterine serous carcinomas are an aggressive minority of endometrial cancers. They are characterized by mutations in TP53 and extensive copy number alterations and are primarily classified in the copy number-high/p53abn molecular prognostic group, highlighting a unique molecular profile that is crucial for understanding their behavior and treatment responses. Clinical studies have shown that molecular categorization via biomarkers can facilitate proper treatment selection, and this is now widely used. In this context, the scope of this systematic review is to identify molecular characteristics with prognostic significance for these neoplasms to further inform on their treatment needs. We performed a comprehensive literature search of all articles written in English using the PubMed/Medline and Cochrane databases through February 2025. Our review led to the inclusion of 95 studies, from which we identified a total of 66 distinct molecular characteristics along with new cancer signatures that may impact prognosis. These findings have the potential to inform clinical practice by aiding in the development of tailored treatment strategies for patients with uterine serous carcinoma, ultimately improving outcomes in this challenging malignancy.