Brain tumors are a heterogeneous group of brain neoplasms that are highly prevalent in individuals of all ages worldwide. Within this pathological framework, the most prevalent and aggressive type of primary brain tumor is glioblastoma (GB), a subtype of glioma that falls within the IV-grade astrocytoma group. The death rate for patients with GB remains high, occurring within a few months after diagnosis, even with the gold-standard therapies now available, such as surgery, radiation, or a pharmaceutical approach with Temozolomide. For this reason, it is crucial to continue looking for cutting-edge therapeutic options to raise patients’ survival chances. Pentraxin 3 (PTX3) is a multifunctional protein that has a variety of regulatory roles in inflammatory processes related to extracellular matrix (ECM). An increase in PTX3 blood levels is considered a trustworthy factor associated with the beginning of inflammation. Moreover, scientific evidence suggested that PTX3 is a sensitive and earlier inflammation-related marker compared to the short pentraxin C-reactive protein (CRP). In several tumoral subtypes, via regulating complement-dependent and macrophage-associated tumor-promoting inflammation, it has been demonstrated that PTX3 may function as a promoter of cancer metastasis, invasion, and stemness. Our review aims to deeply evaluate the function of PTX3 in the pathological context of GB, considering its pivotal biological activities and its possible role as a molecular target for future therapies.

Multiple myeloma (MM) is a currently incurable hematologic cancer. This disease is characterized by immunological alterations of myeloid cells and lymphocytes. The first-line therapy involves the use of classic chemotherapy; however, many patients have a relapsed form that could evolve into a refractory MM. The new therapeutic frontiers involve the use of new monoclonal antibodies (Mab) such as daratumumab, isatuximab, and elotuzumab. In addition to monoclonal antibodies, new immunotherapies based on modern bispecific antibodies and chimeric antigen receptor (CAR) T cell therapy have been investigated. For this reason, immunotherapy represents the greatest hope for the treatment of MM. This review intends to focus the attention on the new approved antibody targets. The most important are: CD38 (daratumumab and isatuximab), SLAM7 (elotuzumab), and BCMA (belantamab mafodotin) for the treatment of MM currently used in clinical practice. Although the disease is still incurable, the future perspective is to find the best therapeutic combination among all available drugs.

Background: The introduction of immunotherapy has significantly improved survival outcomes in many solid tumors. However, a subset of patients exhibits limited responsiveness to immune checkpoint inhibitors (ICIs). Emerging evidence indicates that the gut microbiota plays a critical role in modulating the effectiveness of immunotherapy. Consequently, the concurrent use of certain medications that disrupt microbial diversity may contribute to reduced treatment efficacy. Among the agents implicated in altering the gut microbiota are antibiotics and proton pump inhibitors (PPIs). Methods: A systematic literature search was conducted in PubMed, Scopus, and EMBASE. Eligible studies assessed the association between PPI use and progression-free survival (PFS) and/or overall survival (OS) in patients with solid tumors receiving ICIs. They reported hazard ratios (HRs) with 95% confidence intervals (CIs). The analysis focused on studies published between November 2022 and January 2025, in continuity with prior comprehensive meta-analyses that included studies up to November 2022. This contiguity-based approach enabled a focused evaluation of recent evidence, minimizing redundancy while allowing for the detection of evolving trends in clinical practice and methodology. Data were synthesized using both fixed-effects and random-effects models and visualized via Forest plots. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) and the Newcastle–Ottawa Scale (NOS). Between-study heterogeneity and publication bias were evaluated using I² statistics and funnel plots. Results: From a pool of over 400 screened articles between November 2022 and January 2025, seven studies met the inclusion criteria. The PFS analysis incorporated data from 1367 participants, while the OS analysis included 10,420 individuals. Use of PPIs was linked to a 12% higher risk of disease progression (HR = 1.12; 95% CI: 0.90–1.34) and an 18% increased mortality risk (HR = 1.18; 95% CI: 1.11–1.25). Conclusions: The observed association between PPIs exposure and reduced efficacy of ICIs, as reflected in worsened PFS and OS outcomes, highlights a potential clinical concern that merits further investigation in prospective studies.

Rhodesain is a cysteine protease that is crucial for the life cycle of Trypanosoma brucei rhodesiense, a parasite causing the lethal form of Human African Trypanosomiasis. CD24 is a recently developed synthetic inhibitor of rhodesain, characterized by a nanomolar affinity towards the trypanosomal protease (K_i = 16 nM), and acting as a competitive inhibitor. In the present work, we carried out a combination study of CD24 with curcumin, the multitarget nutraceutical obtained from Curcuma longa L., which we demonstrated to inhibit rhodesain in a non-competitive manner. By applying the Chou and Talalay method, we obtained an initial additive effect at IC₅₀ (f_a = 0.5, Combination Index = 1), while for the most relevant f_a values, ranging from 0.6 to 1, i.e., from 60% to 100% of rhodesain inhibition, we obtained a combination index < 1, thus suggesting that an increasingly synergistic action occurred for the combination of the synthetic inhibitor CD24 and curcumin. Furthermore, the combination of the two inhibitors showed an antitrypanosomal activity better than that of CD24 alone (EC₅₀ = 4.85 µM and 10.1 µM for the combination and CD24, respectively), thus suggesting the use of the two inhibitors in combination is desirable.

Brain tumors are a diverse collection of neoplasms affecting the brain with a high prevalence rate in people of all ages around the globe. In this pathological context, glioblastoma, a form of glioma that belongs to the IV-grade astrocytoma group, is the most common and most aggressive form of the primary brain tumors. Indeed, despite the best treatments available including surgery, radiotherapy or a pharmacological approach with Temozolomide, glioblastoma patients’ mortality is still high, within a few months of diagnosis. Therefore, to increase the chances of these patients surviving, it is critical to keep finding novel treatment opportunities. In the past, efforts to treat glioblastoma have mostly concentrated on customized treatment plans that target specific mutations such as epidermal growth factor receptor (EGFR) mutations, Neurotrophic Tyrosine Receptor Kinase (NTRK) fusions, or multiple receptors using multi-kinase inhibitors like Sunitinib and Regorafenib, with varying degrees of success. Here, we focused on the receptor tyrosine kinase AXL that has been identified as a mediator for tumor progression and therapy resistance in various cancer types, including squamous cell tumors, small cell lung cancer, and breast cancer. Activated AXL leads to a significant increase in tumor proliferation, tumor cell migration, and angiogenesis in different in vitro and in vivo models of cancer since this receptor regulates interplay with apoptotic, angiogenic and inflammatory pathways. Based on these premises, in this review we mainly focused on the role of AXL in the course of glioblastoma, considering its primary biological mechanisms and as a possible target for the application of the most recent treatments.

The gut–brain axis refers to the bidirectional communication network linking the gut microbiota and the central nervous system (CNS). Recent research has highlighted the critical role of gut microbiota in influencing brain health, neurogenesis, and neuroinflammation. In the context of brain tumors, especially gliomas, the gut–brain axis plays a significant role in tumor development, progression, and response to therapy. Gut dysbiosis, characterized by an imbalance in microbiota composition, has been linked to chronic inflammation, immune suppression, and altered blood–brain barrier (BBB) permeability, key factors in glioma pathogenesis. Gut-derived metabolites such as short-chain fatty acids (SCFAs) and neurotransmitters can either promote or inhibit tumor growth, impacting the tumor microenvironment (TME) and immune responses. Emerging evidence suggests that microbiome modulation, through strategies such as probiotics, prebiotics, and dietary interventions, may enhance anti-tumor immunity and improve the efficacy of conventional treatments like chemotherapy, radiotherapy, and immunotherapy. This review examines the interactions between gut microbiota and brain tumors, focusing on how microbiota alterations may influence tumor biology and therapeutic outcomes. Understanding the mechanisms of the gut–brain axis could lead to novel adjunctive therapies in neuro-oncology, offering new prospects for personalized treatment strategies in brain tumor management.