Immunotherapy has emerged as a transformative approach in gastrointestinal (GI) cancers, addressing historically poor survival rates in advanced-stage disease. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis demonstrate remarkable efficacy in colorectal cancer with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), exemplified by trials like NICHE-2 achieving exceptional pathological response rates. However, significant limitations persist, including resistance in some dMMR/MSI-H tumors, minimal efficacy in proficient mismatch repair (pMMR) tumors, and low overall response rates across most GI malignancies due to tumor heterogeneity and immune evasion mechanisms. Predictive biomarkers such as tumor mutational burden (TMB) and PD-L1 expression are crucial for optimizing patient selection, while hypermutated pMMR tumors with POLE mutations represent emerging therapeutic opportunities. In pancreatic adenocarcinoma, where survival remains dismal, combination strategies with chemotherapy and novel approaches like cancer vaccines show promise but lack transformative breakthroughs. Esophagogastric cancers benefit from ICIs combined with chemotherapy, particularly in MSI-H and HER2-positive tumors, while hepatocellular carcinoma has achieved significant progress with combinations like atezolizumab–bevacizumab and durvalumab–tremelimumab surpassing traditional therapies. Biliary tract cancers show modest improvements with durvalumab–chemotherapy combinations. Despite these advances, immunotherapy faces substantial challenges including immune-related adverse events, acquired resistance through cancer immunoediting, and the need for biomarker-driven approaches to overcome tumor microenvironment barriers. This review discusses key clinical trials, therapeutic progress, and emerging modalities including CAR T-cell therapies and combination strategies, emphasizing the critical need to address resistance mechanisms and refine precision medicine approaches to fully realize immunotherapy’s potential in GI malignancies.

Breast cancer is the most common cancer in a woman with a five-year survival of patients with metastatic disease is estimated at 23%. Ado-trastuzumab emtansine (T-DM1) is a HER2-antibody drug conjugate currently approved for the treatment of HER2-positive pre-treated metastatic breast cancer (BC). We report a case of recurrent metastatic breast cancer with unusually lengthy progression-free survival (PFS) on T-DM1 chemotherapy. She was diagnosed with Triple Positive Stage IIIC multifocal invasive ductal carcinoma of the left breast. After completing neoadjuvant chemotherapy, she underwent a bilateral mastectomy. Final pathology showed partial response. Postoperatively, she received adjuvant chemotherapy and radiation therapy. She was started on Q21 days trastuzumab following completion of adjuvant chemotherapy. Systemic imaging showed liver lesions and biopsy confirmed recurrence. She was started on T-DM1, endocrine therapy with anastrozole was continued. She is currently status post 45 cycles. T-DM1 was approved for the treatment (single-agent) of HER2-positive, metastatic BC based on phase III data from the EMILIA and TH3RESA study. Median PFS in the T-DM1 arm was 9.6 months. Herein, we present a case of a woman with recurrent triple positive metastatic BC with a lengthy progression-free survival on T-DM1 chemotherapy.

Background : Metabolic syndrome (MetS) is a significant global health burden and a known risk factor of cardiovascular disease and diabetes. Growing evidence also links MetS to cancer development, likely via chronic inflammation, insulin resistance, and hormone disruption. However, its association with laryngeal cancer remains largely unclear and underexplored. Methods: For this review, we thoroughly searched PubMed/MEDLINE, Scopus, and Web of Science for observational studies investigating associations of MetS with laryngeal or head and neck cancers (HNCs) until 1 August 2025. Five large population-based studies were found to meet inclusion criteria, and risk of bias was assessed using the Joanna Briggs Institute checklist (JBI). Results: Three Korean cohort studies consistently found that MetS increased the risk of laryngeal cancer (HR 1.13–1.32), independent of smoking and alcohol use. Hypertension and hyperglycemia were the most consistent components associated with increased risk, and chronic MetS conferred the highest hazard. In contrast, analyses from the UK Biobank (HNC) and SEER-Medicare (HNSCC) cohorts showed null and inverse associations, respectively. Additional findings included dose–response effects with increasing MetS components, U-shaped associations for HDL-C and waist circumference and increased risk associated with elevated C-reactive protein. Conclusions: Current evidence suggests a possible association between MetS and risk of laryngeal cancer, although the direction and strength of effect vary across populations. Findings from Korean cohorts provide consistent signals of increased risk, whereas Western datasets have not replicated this pattern. Overall, the certainty of evidence is low to moderate, warranting cautious interpretation and further validation in diverse populations before inferring causality.