Undoubtedly, the development of COVID-19 vaccines displays a critical step towards ending this devastating pandemic, considering their protective benefits in the general population. Yet, data regarding their efficacy and safety in cancer patients are limited. Herein we provide the initial analysis of immune responses after the first dose of vaccination in 21 breast cancer patients receiving cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. The levels of neutralizing antibodies post vaccination were similar to the matched healthy controls, whereas no safety issues have been raised. Further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.
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.
Data regarding the safety and efficacy of COVID-10 vaccines among cancer patients are lacking. Factors such as age, underlying disease and antineoplastic treatment confer negatively to the immune response due to vaccination. The degree of immunosuppression though may be lessen by targeted treatments like the androgen receptor-targeted agents (ARTA) that are commonly used in patients with metastatic prostate cancer. Herein, we report our data on 25 patients with prostate cancer under treatment with ARTA who were vaccinated for COVID-19. Our data suggest that these patients develop neutralizing antibodies against SARS-CoV-2 similarly to healthy volunteers. No safety issues were noted.
Recent advances in glioblastoma (GB) research have shed light on the molecular characteristics, the defected intracellular signaling pathways, and the genetic and epigenetic alterations involved in their pathogenesis. Despite constant efforts, GB remains an aggressive malignant tumor with limited therapeutic approaches, poor prognosis, and a low survival rate. Emerging evidence points towards the crucial impact of epigenetic post-translational modifications in cancer development with emphasis on the regulatory role of histone deacetylation in several key cellular processes, including metabolic pathways, regulation of stress response, senescence, proliferation, DNA repair, and apoptosis. The silent information regulator proteins (Sirtuins) are deacetylases of histone and non-histone proteins that have been recently implicated in the initiation as well as in the progression of GB. Herein, we provide a critical overview of the emerging functional role and mechanism of action of the seven Sirtuins (SIRT1-7) in GB and discuss their potential targeting options in clinical practice.
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.
170 Background: Molecular testing for mutations in genes related to homologous recombination repair (HRR) and microsatellite instability (MSI) is suggested for patients with advanced prostate cancer by international guidelines. Recently, olaparib has been approved for patients with metastatic castration resistant prostate cancer patients that bear mutations in BRCA1/2 genes in Europe. In Greece, molecular testing for prostate cancer patients is not reimbursed. In this setting we describe our experience from investigating the molecular profile of patients with advanced/metastatic disease. Methods: We retrospectively collected clinicopathological data of patients treated in our center for advanced/metastatic prostate cancer whose tumours were subjected to whole exome sequencing analysis for a panel of 58 genes including BRCA1/2. All patients provided written informed consent and the study was approved by the local ethics committee. Results: Tumor samples from 37 patients with advanced or metastatic prostate cancer were analyzed. Median age of the patients was 60.2 years (25th-75th percentile 54.4-63.9 years) and most of them (19/37, 51.4%) were presented with de novo metastatic disease. Clinicopathological characteristics of the patients are presented in the table. Eight samples (21.6%) were evaluated as inadequate to perform further analysis. In the remaining 29 cases, no BRCA1/2 mutations were detected. Instead, 7 patients had mutations in HRR-related genes, including 3 patients with ATM mutations, two in CHEK2, one in CHEK1 and one in RAD50. TP53 mutations were found in 8 patients (21.6%) and PTEN mutations in 2 (5.4%). Newer Hormonal Treatments were used as first-line treatment in mCRPC in 24 patients (64.9%), while 6 received docetaxel. Median PFS in first-line mCRPC was 12.0 months (95% CI 9.7-14.3) in the whole population and did not differ significantly in patients with HRD mutations (11.8 months) or TP53 mutations (11.8 months). Two patients with ATM mutations received olaparib as fourth and fifth line of treatment respectively with stable disease as best response. Conclusions: Biomarker driven targeted therapies are currently available for mCRPC patients. In our cohort, molecular testing was negatively affected by the poor quality of archival tissues in a significant percentage of patients. However, mutations in HRR-related genes were found in almost 20% of patients with possible therapeutic implications. Therefore, it is necessary to have a reimbursed molecular testing for prostate cancer patients in Greece.[Table: see text]
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