Molecularly guided therapy in gastrointestinal malignancies: From established targets to resistance and emerging precision strategies

Table 1 Literature search strategy used for the narrative review

Component	Description
Review type	Narrative review
Databases	PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar
Search period	January 2000 to July 30, 2026
Language	English
Search approach	Structured keyword-based searches using Boolean operators (AND/OR), with MeSH terms used where applicable
Core search terms	“Gastrointestinal cancer”, “gastrointestinal malignancy”, “targeted therapy”, “molecular targeted therapy”, and “precision oncology”
Cancer-specific terms	Esophageal cancer, gastric cancer, gastroesophageal junction cancer, colorectal cancer, pancreatic cancer, hepatocellular carcinoma, cholangiocarcinoma, biliary tract cancer, and GIST
Molecular target terms	EGFR, HER2, VEGF, FGFR, KIT, PDGFRA, BRAF, KRAS, IDH1, CLDN18.2, FGFR2b, PARP, NTRK, RET, MET, ALK, ROS1, PI3K, AKT, and mTOR
Additional therapeutic terms	Antibody-drug conjugates, bispecific antibodies, DNA damage repair, genomic profiling, next-generation sequencing, and liquid biopsy
Additional searches	Cancer-specific and drug-specific searches addressing pivotal trials, regulatory evidence, resistance mechanisms, and emerging therapies
Evidence prioritized	Randomized clinical trials, phase II/III studies, prospective studies, meta-analyses, international guidelines, landmark trials, and high-quality reviews
Study selection	Studies were selected based on relevance, methodological quality, clinical significance, molecular specificity, and contribution to established or emerging targeted treatment
Screening process	Independent screening of titles and abstracts, followed by full-text assessment by two reviewers
Disagreement resolution	Discussion and consensus, with consultation of a third reviewer when required
Evidence synthesis	Narrative synthesis organized by gastrointestinal malignancy and molecular target, addressing mechanism of action, clinical role, evidence maturity, biomarkers, resistance mechanisms, and emerging strategies
Evidence grading	Grade A: Randomized phase III evidence and/or established standard-of-care treatment. Grade B: Prospective phase II evidence or substantial clinical evidence. Grade C: Early-phase, retrospective, or otherwise limited clinical evidence. Grade D: Preclinical or experimental evidence

MeSH: Medical Subject Headings; GIST: Gastrointestinal stromal tumor; EGFR: Epidermal growth factor receptor; HER2: Human epidermal growth factor receptor 2; VEGF: Vascular endothelial growth factor; FGFR: Fibroblast growth factor receptor; PDGFRA: Platelet-derived growth factor receptor alpha; PARP: Poly (ADP-ribose) polymerase; NTRK: Neurotrophic tyrosine receptor kinase; RET: Rearranged during transfection; MET: Mesenchymal-epithelial transition factor; ALK: Anaplastic lymphoma kinase; ROS1: ROS proto-oncogene 1; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; mTOR: Mechanistic target of rapamycin; KIT: KIT proto-oncogene receptor tyrosine kinase; CLDN18.2: Claudin 18.2.