BRCA-associated hereditary male cancers: can gender affect the prevalence and spectrum of germline pathogenic variants?

Introduction: Although hereditary male neoplasms are quite rare, individuals harbouring germline BRCA1/2 pathogenic variants (PVs) may have a risk of developing tumours associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, including male breast (MBC), prostate (PCa) and pancreatic (PC) cancers, and melanoma. Women and men showed a comparable genetic architecture of cancer susceptibility, but there are some gender-specific features. Since little is known about cancer genetic susceptibility in male population, our study was aimed at investigating the frequency of BRCA1/2 PVs in men with HBOC syndrome-associated tumors, in order to understand whether differences in gender may reflect in the prevalence and spectrum of germline alterations. Patients and methods: We retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the "Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults" of the University-Hospital Policlinico "P. Giaccone" of Palermo (Italy). Results: Our investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing. Discussion: Our study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care.

Clinical relevance of exosome-derived microRNAs in Ovarian Cancer: Looking for new tumor biological fingerprints.

Specific tumor-derived extracellular vesicles, called exosomes, are considered as potential key players in cross-talk between immune system and tumor microenvironment in several solid tumors. Different studies highlighted the clinical relevance of exosomes in ovarian cancer (OC) for their role in early diagnosis, prognosis, chemoresistance, targeted therapy. The exosomes are nanosize vesicles carrying lipids, proteins, and nucleic acids. In particular, exosomes shuttle a wide spectrum of microRNAs (miRNAs) able to induce phenotypic reprogramming of target cells, contributing to tumor progression. In this review, we will discuss the promising role of miRNAs shuttled by exosomes, called exosomal miRNAs (exo-miRNAs), as potential biomarkers for early detection, tumour progression and metastasis, prognosis, and response to therapy in OC women, in order to search for new potential biological fingerprints able to better characterize the evolution of this malignancy and provide a clinically relevant non-invasive approach useful for adopting, in future, personalized therapeutic strategies.

Monoclonal antibodies for the treatment of non-hematological tumors: a safety review.

Introduction: The introduction of monoclonal antibodies (moAbs) into clinical practice revolutionized the treatment strategies in several solid tumors. These agents differ from cytotoxic chemotherapy for their mechanism of action and toxicity. By targeting specific antigens present on healthy cells and modulating immune system activity, these biological drugs are able to generate a wide spectrum of peculiar adverse events that can negatively impact on patients' quality of life. Areas covered: In this review, the main side effects associated with the use of moAbs have been described to show their incidence and current management strategies, which may drive clinicians in their daily practice. Expert opinion: The majority of these drugs represents an example of successful innovation, since they are able to induce a significant improvement of patients' survival and quality of life without any increase in related side effects as compared to standard cancer treatments. For this reason, they have become new milestones in personalized therapy for different non-hematological malignancies. With the increasing use of moAbs in treatment regimens, it is strongly recommended that clinicians are knowledgeable about the side effects associated with these agents, their management and monitoring, to optimize the clinical treatment of cancer patients.

Linking patterns and processes across scales: the application of scale-transition theory to algal dynamics on rocky shores.

Understanding how species and environments respond to global anthropogenic disturbances is one of the greatest challenges for contemporary ecology. The ability to integrate modeling, correlative and experimental approaches within individual research programs will be key to address large-scale, long-term environmental problems. Scale-transition theory (STT) enables this level of integration, providing a powerful framework to link ecological patterns and processes across spatial and temporal scales. STT predicts the large-scale (e.g. regional) behavior of a system on the basis of nonlinear population models describing local (e.g. patch-scale) dynamics and the interaction between these nonlinearities and spatial variation in population abundance or environmental conditions. Here we use STT to predict the dynamics of turf-forming algae on rocky shores at Capraia Island, in the northwest Mediterranean. We developed a model of algal turf dynamics based on density-dependent growth that included the effects of local interactions with canopy algae. The model was parameterized with field data and used to scale up the dynamics of algal turfs from the plot scale (20×20 cm) to the island scale (tens of km). The interaction between nonlinear growth and spatial variance in cover of turfing algae emerged as a key term to translate the local dynamics up to the island scale. The model successfully predicted short-term and long-term mean values of turf cover estimated independently from a separate experiment. These results illustrate how STT can be used to identify the relevant mechanisms that drive large-scale changes in ecological communities. We argue that STT can contribute significantly to the connection between biomechanics and ecology, a synthesis that is at the core of the emerging field of ecomechanics.