Despite a recent overall decrease in colorectal cancer (CRC) incidence and mortality, there has been a significant rise in CRC diagnoses in young adults. Early onset colorectal cancer (EOCRC) is defined as CRC diagnosed before the age of 50. Possible predisposing conditions include not only genetic syndromes but also other risk factors, such as microbiome alteration, antibiotic exposure, obesity, diabetes mellitus, and inflammatory bowel disease. EOCRC tends to be diagnosed later than in the older counterpart because of a lack of awareness and the fact that screening for CRC usually starts at the age of 50. Furthermore, CRC in young adults seems to be related to unique molecular features and more aggressive clinical behavior. This paper aims to provide an in-depth review of this poorly understood subject, with a comprehensive review of the state of the art and considerations for future perspectives.

Neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasms that originate from neuroendocrine cells, characterized by their ability to secrete hormones and peptides. Once considered rare, the incidence of NETs has steadily increased due to improved diagnostic modalities. The therapeutic landscape is multifaceted, ranging from surgery for localized disease to pharmacological interventions for advanced cases. However, the absence of robust predictive biomarkers precludes patient stratification and optimization of therapy. Everolimus, an oral mTOR inhibitor, has emerged as a key therapeutic agent due to its dual role in inhibiting cell proliferation and angiogenesis. Nevertheless, challenges such as resistance mechanisms, toxicity and optimal treatment sequencing remain unresolved. This article provides a comprehensive review of the role of everolimus in the management of NETs, focusing in particular on unresolved issues, from the absence of predictive biomarkers to the unavailability of defined guidelines for determining the correct therapeutic sequence.

Metastatic colorectal cancer (mCRC) remains a major cause of cancer-related mortality worldwide and requires the development of new biomarkers to improve patient management. Traditional markers, such as RAS mutations and microsatellite instability (MSI), have revolutionized therapeutic decisions, but emerging evidence underlines the importance of integrating multi-omics sciences for a deeper understanding of tumor biology and therapeutic resistance. Although these omics technologies hold great promise for the advancement of precision oncology, significant challenges remain. However, the integration of multi-omics data is opening the way to more accurate diagnostics, personalized therapies, and improved outcomes for mCRC patients. This review provides an in-depth description of the various omics sciences and explores their advantages and critical issues.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely arising in the setting of chronic liver disease and cirrhosis. Given the immunosuppressive hepatic tumor microenvironment, optimizing immunotherapeutic strategies is critical to improving patient outcomes. This review examines the biological rationale and clinical evidence supporting dual immune checkpoint inhibition with nivolumab plus ipilimumab in advanced HCC. We discuss mechanisms of immune tolerance in cirrhosis and tumor progression, including regulatory T cells, myeloid-derived suppressor cells, hypoxia, metabolic reprogramming, and T-cell exhaustion. Key clinical data from early-phase studies, such as CheckMate 040 and the phase III CheckMate 9DW, are analyzed, focusing on overall survival, response rates, and durability of response compared with tyrosine kinase inhibitors. A structured literature search of PubMed, Embase, and major oncology congress proceedings was conducted to identify relevant preclinical and clinical studies. Dual checkpoint blockade represents an effective first-line option for selected patients with advanced HCC, offering meaningful survival benefit at the cost of increased immune-related toxicity. Future progress depends on improved patient selection, biomarker development, and rational combination strategies.

Background: Early-onset colorectal cancer represents a growing global health challenge. Although differences between young and elderly patients are recognized, direct comparison of extreme age groups may further characterize their distinct clinical and therapeutic profiles. Methods : This is a retrospective, single-centre, observational study, comparing young patients (Group A: ≤50 years, n = 153) with elderly patients (Group B: ≥75 years, n = 533) during the period 1990–2025. Results: Group A presented higher rates of stage IV presentation (66.9% vs. 47.1%, p < 0.001), T4 tumors, N2 nodal involvement, distal tumor localization and synchronous metastasis (87.5% vs. 70.6%, p = 0.001), predominantly involving the liver and peritoneum. Younger patients received more intensive adjuvant and metastatic systemic treatment. The mOS was 52.8 months for Group A compared to 26.4 months for Group B (HR 2.29, 95% CI 1.57–3.54, p < 0.001) and DFS was longer in Group A (28.6 vs. 19.1 months; HR 2.26, 95% CI 1.55–3.29, p < 0.001). No statistically significant differences were observed in first- or second-line PFS between the cohorts. Conclusions: Early-onset colorectal cancer exhibits a more adverse clinicopathological profile. Younger patients showed longer overall and disease-free survival in this cohort, although these findings should be interpreted with caution given potential differences in treatment exposure, baseline fitness, comorbidity burden and the substantial temporal heterogeneity of the study period.