Gastrointestinal Cancer

P=N/A, N=140, Active, not recruiting, Cumhuriyet University

P2, N=25, Recruiting, Ohio State University Comprehensive Cancer Center

P=N/A, N=60, Recruiting, Institute of Oncology Ljubljana

P2, N=46, Not yet recruiting, Kumquat Biosciences Inc.

P=N/A, N=103, Not yet recruiting, Erasmus Medical Center

P1, N=18, Recruiting, Beijing GoBroad Hospital | Not yet recruiting --> Recruiting

P=N/A, N=60, Recruiting, Institute of Oncology Ljubljana

P3, N=129, Recruiting, Intergroupe Francophone de Cancerologie Thoracique | Not yet recruiting --> Recruiting | Trial completion date: Mar 2030 --> Aug 2030 | Initiation date: Sep 2025 --> Feb 2026 | Trial primary completion date: Sep 2028 --> Feb 2029

P=N/A, N=72, Active, not recruiting, University of Oklahoma | Trial primary completion date: Dec 2025 --> Dec 2026

Emerging evidence links salvage metabolism to tumor progression, where incorporation of salvage-derived nucleotides may contribute to unexplainable mutational signatures detected in cancers, such as gastrointestinal cancer. Recognizing salvage as a hidden source of mutagenesis reshapes our understanding of genome instability and provides potential opportunities for disease prevention, diagnosis, and therapeutic intervention.

Targeted tyrosine kinase inhibitors (TKIs) have transformed GIST management, with imatinib as the foundational first-line therapy and subsequent agents, sunitinib, regorafenib, avapritinib, and ripretinib, addressing primary or secondary resistance driven by diverse mutational patterns. Emerging therapeutic directions include next-generation kinase inhibitors, heat shock protein inhibitors, immunotherapy, metabolic and epigenetic targeting, and biomarker-driven individualized treatment strategies. This review synthesizes contemporary advances in the histopathological, molecular, and therapeutic landscape of GISTs, emphasizing an integrated diagnostic approach and highlighting ongoing efforts to overcome therapeutic resistance and optimize personalized care.

The patient was started on capecitabine and oxaliplatin in addition to trastuzumab with subsequent clinical and radiological improvement. Unresectable, metastatic HER2 positive conventional adenocarcinoma is being managed using platinum-fluoropyrimidine doublet therapy with anti-HER2 monoclonal antibody trastuzumab. This case report calls for aggressive IHC staining for prompt diagnosis where necessary as well as proper guidelines for management.