Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC.

Hepatocellular carcinoma (HCC), the most common primary liver malignancy and the sixth most common cancer globally, remains fatal for many patients with inappropriate responses to treatment. Recent advancements in immunotherapy have transformed the treatment landscape for advanced HCC. However, variability in patient responses to immunotherapy highlights the need for biomarkers that can predict treatment outcomes. This manuscript comprehensively reviews the evolving role of biomarkers in immunotherapy efficacy, spanning from blood-derived indicators—alpha-fetoprotein, inflammatory markers, cytokines, circulating tumor cells, and their DNA—to tissue-derived indicators—programmed cell death ligand 1 expression, tumor mutational burden, microsatellite instability, and tumor-infiltrating lymphocytes. The current body of evidence suggests that these biomarkers hold promise for improving patient selection and predicting immunotherapy outcomes. Each biomarker offers unique insights into disease biology and the immune landscape of HCC, potentially enhancing the precision of treatment strategies. However, challenges such as methodological variability, high costs, inconsistent findings, and the need for large-scale validation in well-powered two-arm trial studies persist, making them currently unsuitable for integration into standard care. Addressing these challenges through standardized techniques and implementation of further studies will be critical for the future incorporation of these biomarkers into clinical practice for advanced HCC.

Gastric cancer (GC) represents a major global health challenge as a highly prevalent disease with high mortality whose global incidence and mortality are predicted to worsen over the coming years. To date, our standard of care for advanced gastric cancer of combination chemotherapy and immunotherapy has a 1-year overall survival rate of 55%. Significant efforts have gone into identifying targetable alterations in gastric cancer, ultimately yielding the Fibroblast Growth Factor Receptors (FGFRs) family, specifically FGFR2 as a promising target. FGFR2 is overexpressed in GC, particularly diffuse-type GC, and is associated with poor prognostic outcomes. In recent years, there has been an increasing number of small molecule inhibitors and monoclonal antibodies targeting FGFR2 that have entered into clinical trials. Specifically for GC, these agents are currently being trialed in various phases as monotherapies or with standard-of-care treatments to make a clinically meaningful impact on what appears to be an important biological axis of GC. In this review, we outline the underlying biology of FGFR2, its putative role in GC, and the various FGFR2-targeted agents currently in clinical trials for gastric cancer patients as well as postulate some challenges in adopting these therapeutics for clinically meaningful benefit.

Background: Hepatocellular carcinoma (HCC) is a prevalent liver cancer with poor prognosis, often linked to hepatitis B (HBV) and C (HCV) infections. This meta-analysis evaluates the efficacy of immunotherapy in HCC, particularly in cases arising from viral hepatitis. Methods: In adherence to PRISMA Statement 2020 guidelines, the immunotherapeutic outcomes comprised objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Data were analyzed from randomized controlled trials up to April 2024 using the fixed-effects models in R (V.4.3.3.) and RevMan (Cochrane). Results: This study included 9 trials with 5316 patients. The ORR was slightly higher in the viral group at 27.93% compared to 24.07% in the non-viral group, though this difference was not significant (p = 0.15). Viral HCC patients exhibited a median PFS of 7.3 months (IQR: 6.2–8.4) compared to 5.8 months (IQR: 5.48–6.13) in non-viral patients, a significant improvement (p = 0.005). Similarly, median OS was longer in the viral group at 16.8 months (IQR: 12.99–20.61) versus 15.2 months (IQR: 13.25–17.15) for non-viral HCC, which was also significant (p < 0.0001). The median OS for viral HCC was 16.8 months (IQR: 14.11–19.49 months), with HBV patients experiencing slightly higher survival at 17.15 months (IQR: 14.3–20 months) compared to 16.8 months (IQR: 12.99–20.61 months) for HCV patients; this difference was not statistically significant (p = 0.89). Conclusions: Immunotherapy shows potential in treating HCC, with significantly better outcomes in viral HCC, particularly HBV-associated cases. The heterogeneity highlights the need for personalized treatment approaches based on the viral background of HCC patients. Further research should aim to optimize these therapies to improve survival rates.