Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis.

Evidence of β-blockers drug repurposing for the treatment of triple negative breast cancer: A systematic review

Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses. Age-associated decline in sex steroid hormone levels may mediate proinflammatory reactions in older adults, thereby increasing their risk of adverse outcomes, whereas sex hormones and/or sex hormone receptor modulators may attenuate the inflammatory response and provide benefit to COVID-19 patients. While multiple pharmacological options including anticoagulants, glucocorticoids, antivirals, anti-inflammatory agents and traditional Chinese medicine preparations have been tested to treat COVID-19 patients with varied levels of evidence in terms of efficacy and safety, information on sex-targeted treatment strategies is currently limited. Women may have more benefit from COVID-19 vaccines than men, despite the occurrence of more frequent adverse effects, and long-term safety data with newly developed vectors are eagerly awaited. The prevalent inclusion of men in randomized clinical trials (RCTs) with subsequent extrapolation of results to women needs to be addressed, as reinforcing sex-neutral claims into COVID-19 research may insidiously lead to increased inequities in health care. The huge worldwide effort with over 3000 ongoing RCTs of pharmacological agents should focus on improving knowledge on sex, gender and age as pillars of individual variation in drug responses and enforce appropriateness.

Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about the safety of these drugs in pediatric patients is partially assessed. The aim of this study was to evaluate the safety of AADs in pediatric patients with solid tumors. Clinical trials and observational studies were searched in PubMed, ISI Web of Science, and ClinicalTrials database For each included study, adverse events (AEs) were extracted. A meta-analysis was conducted by pooling proportions of AEs using a random intercept logistic regression model. Seventy studies were retrieved. Most part were clinical trials (55 out of 70), and only fifteen observational studies were found. Overall, proportion of serious and non-serious AEs of AADs used as monotherapy was 46% and 89%, respectively. Proportions of serious AEs varied among drugs: sunitinib, 79%; lenvatinib, 64%; sorafenib, 48%; ramucirumab, 41%; pazopanib, 30%; and vandetanib, 27%. A higher proportion of non-serious hematological AEs was found in the patients receiving pazopanib with respect to sunitinib and lenvatinib. The safety profile of AADs has been extensively investigated for mostly drugs in phase I and II trials and is limited to acute toxicities. Overall, one out of two patients using AAD drugs in monotherapy experienced a serious AE despite proportions varied per single drugs. When AADs were combined with standard chemotherapy, the proportion of AEs varied in relation to the single combinations.

Repurposing of drugs for triple negative breast cancer: an overview Andrea Spini1,2, Sandra Donnini3, Pan Pantziarka4, Sergio Crispino4,5 and Marin

Switch patterns among different biologics and from originators to biosimilars (and vice versa) can be complex in patients with psoriasis (PsO) and psoriatic arthritis (PsA). To describe switching pattern of biological drugs in PsO/PsA patients and to explore predictors of multiple switches and switch-back. A large-scale retrospective cohort study was conducted using the Italian VALORE database. Bio-naïve users treated for PsO/PsA during 2010-2022 were included. Time to switch/swap and predictors of multiple switches and switch-back were analyzed. 30,700 bio-naïve users were included. At 3 and 5 years of follow-up, patients with at least one switch/swap were 37.1% and 47.8%, respectively. The median time to first switch/swap was significantly shorter (p-value:<0.001) for TNF-α inhibitors (2,068 days) than anti-IL (2,780 days). At one year of follow-up patients starting with IL-23 switched/swapped biological therapy less frequently than those with anti-IL-12/23 and anti-IL-17 (4.9% vs. 8.7% and 9.4%, respectively). Patients starting with anti-IL-12/23 reported a significantly lower risk of multiple switches and switch-back (0.74, 95%CI: 0.67-0.83; 0.58, 95%CI:0.44-0.77, respectively) than those with TNF-α inhibitors. Patients with PsO/PsA starting with TNF-α inhibitors switch/swap more rapidly and frequently than those with anti-IL, which are also associated with a reduced risk of multiple switches during follow-up.