Immunotherapy and chemoimmunotherapy are standard treatments for non-oncogene-addicted advanced non-small cell lung cancer (NSCLC). Currently, a limited number of biomarkers, including programmed death-ligand 1 (PD-L1) expression, microsatellite instability (MSI), and tumor mutational burden (TMB), are used in clinical practice to predict benefits from immune checkpoint inhibitors (ICIs). It is therefore necessary to search for novel biomarkers that could be helpful to identify patients who respond to immunotherapy. In this context, research efforts are focusing on different cells and mechanisms involved in anti-tumor immune response. Herein, we provide un updated literature review on the role of eosinophils in cancer development and immune response, and the functions of some cytokines, including IL-31 and IL-33, in eosinophil activation. We discuss available data demonstrating a correlation between eosinophils and clinical outcomes of ICIs in lung cancer. In this context, we underscore the role of absolute eosinophil count (AEC) and tumor-associated tissue eosinophilia (TATE) as promising biomarkers able to predict the efficacy and toxicities from immunotherapy. The role of eosinophils and cytokines in NSCLC, treated with ICIs, is not yet fully understood, and further research may be crucial to determine their role as biomarkers of response. Artificial intelligence, through the analysis of big data, could be exploited in the future to elucidate the role of eosinophils and cytokines in lung cancer.

Background: Immune checkpoint inhibitors (ICIs) have transformed the management of solid tumors, yet only a subset of patients achieve durable benefit. The gut microbiota is a key modulator of antitumor immunity, and systemic antibiotic therapy (ABT), frequently prescribed—and sometimes overused—in oncology, can profoundly disrupt microbial homeostasis. Observational studies suggest that ABT may impair ICI efficacy, but results remain heterogeneous, warranting an updated synthesis. Methods: We conducted a systematic review and meta-analysis in accordance with the PRISMA 2020 guidelines. PubMed, Scopus, and EMBASE were searched for studies published between 2018 and 2025 evaluating the association between ABT exposure and time-to-event outcomes in patients with solid tumors treated with ICIs. Studies were required to report explicit definition of the ABT exposure window. Random-effects models were considered primary. A sensitivity analysis was performed in non-small cell lung cancer (NSCLC). Results: Fifteen studies encompassing 52,489 patients were included. ABT exposure was associated with significantly worse OS (random-effects HR 1.16, 95% CI 1.03–1.29) and PFS (random-effects HR 1.11, 95% CI 0.95–1.27), indicating an increased risk of death and disease progression compared with no ABT exposure. In the NSCLC sensitivity analysis, ABT was consistently associated with inferior PFS and, when accounting for heterogeneity, with significantly reduced OS, supporting the robustness of the association. Conclusions: ABT administered in temporal proximity to ICIs is associated with clinically meaningful worsening of survival outcomes across solid tumors, consistent with microbiome-mediated impairment of immunotherapy efficacy. These findings support cautious ABT stewardship in patients receiving ICIs and highlight the need for prospective studies integrating microbiome profiling and standardized ABT exposure assessment.

Background: Melanoma is a highly heterogeneous neoplasia in which transcriptional profile encodes much of the biological diversity that determines tumor progression and therapeutic response. To refine its molecular stratification and profiles characterization, we conducted an in silico transcriptomic analysis. Methods: Public microarray datasets from the GEO and ArrayExpress were examined, and the E-MTAB-6697 expression dataset was selected. We used a K-Means clustering algorithm to stratify 194 tumor samples into expression-driven subgroups and analyzed each one to define their transcriptional and biological profiles. Differential expression analysis between identified clusters and controls was performed. Additionally, we applied Weighted-Gene correlation analysis to identify coordinated expression hubs in the tumor dataset and tested the resulting modules for correlation with the identified clusters. Results: Unsupervised clustering of melanoma transcriptomic profiles identified three distinct molecular subtypes characterized by divergent biological programs. While all clusters shared the dysregulation of pathways involved in epidermal differentiation, immune response, and lipid metabolism, they diverged in proliferation, phenotypic plasticity, metabolic adaptation, and apoptotic regulation. Cluster A was characterized by enrichment in DNA replication, repair, and mitochondrial metabolism modules, suggesting a proliferative yet genomically stable state. Cluster B showed enrichment in immune and cytokine signaling pathways alongside reduced proliferative activity, consistent with a quiescent or transitional phenotype. Cluster C displayed coordinated enrichment in cell-cycle, DNA-maintenance, and neuroectodermal reprogramming pathways, indicating a highly plastic and proliferative subtype. Despite these molecular distinctions, all clusters retained an “immunologically hot” profile (IPS 7–8), indicating potential responsiveness to immunotherapy. Conclusions: These findings provide an overview of the functional characteristics of melanoma heterogeneity and identify biological processes that could be targeted by drugs for the development of tailored therapies for each subtype. Nevertheless, future studies in independent clinically annotated cohorts would be required.

Background: Olaparib and niraparib are poly (ADP-ribose) polymerase inhibitors (PARPi) used primarily for the treatment of ovarian cancer. While both drugs have demonstrated efficacy in clinical trials, their safety profiles, particularly in real-world clinical settings, remain to be fully elucidated. Objectives: This study aimed to (i) characterize the adverse drug reactions (ADRs) associated with olaparib and niraparib as reported in the EudraVigilance database, (ii) compare the frequency of the ADRs occurring during treatment with the two drugs, and (iii) compare post-marketing safety data with those from clinical trials. Methods: A retrospective analysis was performed using data from the EudraVigilance database (2017–2024), focusing on individual case safety reports (ICSRs) related to olaparib and niraparib. Descriptive statistics and disproportionality analysis were performed to compare the frequency and severity of reported ADRs. Results: Both olaparib and niraparib had common ADRs including nausea, vomiting, anemia, thrombocytopenia, and fatigue. However, olaparib was associated with a higher risk of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and interstitial lung disease, while niraparib had a higher incidence of gastrointestinal events and thrombocytopenia. Our analysis demonstrates that some specific ADRs, including peripheral neuropathy with niraparib, were reported at higher frequencies compared to clinical trials. The incidence of serious ADRs, including hospitalizations and life-threatening events, was higher with niraparib than with olaparib. Conclusions: This study highlights significant differences in the safety profiles of olaparib and niraparib, with implications for clinical decision-making. Continuous monitoring and personalized management of ADRs are essential to optimize patient outcomes.

Over the past decade, there has been a notable increase in the utilization of immune checkpoint inhibitors in cancer care, transforming the therapeutic landscape for several types of solid tumors. This development has not only expanded the indications for treatment but has also significantly influenced management strategies and prognostic outcomes for specific subsets of cancer patients. In contrast to the general population of cancer patients, individuals diagnosed with both HIV and cancer encounter significant differences in treatment approaches and outcomes. Consequently, this population demonstrates a significantly increased rate of specific mortality for several common types of cancer. Recent studies have reported significant insights into the use of immune checkpoint inhibitors among this patient group. However, the data remain insufficient, and there are still recognized barriers and limitations regarding the use of these agents in cancer patients. Real-world data and reports from clinical practice offer critical perspectives, enabling the sharing of clinical experiences and assisting in navigating complex management decisions. This report outlines two cases of patients with concurrent HIV and cancer who were administered ICIs in diverse clinical settings, highlighting the necessity of cooperation between oncologists and HIV specialists to provide patients with cutting-edge and increasingly tailored treatment options.

KRAS mutations occur in approximately 25-30% of NSCLC cases, with the KRAS G12C substitution present in 10-13% of advanced non-squamous tumors. Historically, KRAS was considered an undruggable oncogene, associated with limited therapeutic options and poor outcomes. The clinical development of KRAS G12C inhibitors has changed this landscape, demonstrating that KRAS can be effectively targeted. Several inhibitors are in clinical development, showing heterogeneous efficacy and safety profiles. Despite clinically meaningful antitumor activity, the durability of benefit achieved with currently available agents remains limited. The therapeutic benefit of currently available KRAS inhibitors is constrained by the emergence of resistance mechanisms, including secondary RAS alterations, activation of bypass signaling pathways, metabolic adaptations, and phenotypic plasticity, leading to early disease progression in a substantial proportion of patients. To address these limitations, next-generation strategies are under active development. ON-state and pan-RAS inhibitors aim to improve suppression of oncogenic signaling and to retain activity in the context of resistance to first-generation compounds. In parallel, multiple combination approaches are being evaluated, including associations with chemotherapy, immune checkpoint inhibitors, and novel pharmacological classes designed to counteract pathway reactivation, enhance response depth and improve clinical benefit. This review provides a comprehensive and updated overview of KRAS G12C inhibition in NSCLC, summarizing biological mechanisms underlying KRAS oncogenesis, clinical evidence supporting currently approved therapies, emerging drug development strategies, mechanisms of therapeutic resistance, and evolving combination approaches. Collectively, these advances are transforming KRAS G12C-mutant NSCLC from a refractory molecular subtype into a disease increasingly amenable to precision oncology strategies.