Personalized Medicine in Gastrointestinal Oncology: A Systematic Review of Targeted Therapies

Abstract

Personalized medicine has revolutionized the treatment landscape for gastrointestinal (GI) oncology by tailoring therapies to individual molecular profiles, thereby improving efficacy and reducing toxicity compared to traditional chemotherapy. This systematic review evaluates the role of targeted therapies in GI cancers, including colorectal, gastric, esophageal, pancreatic, and hepatobiliary malignancies, focusing on key biomarkers such as HER2, EGFR, VEGF, BRAF, KRAS, and MSI status. We conducted a comprehensive search of databases like PubMed, Embase, and Cochrane Library up to August 2025, identifying 13 randomized controlled trials (RCTs) and prospective studies that met inclusion criteria after screening 1,250 records and assessing 215 full-text articles. The included studies, involving over 5,000 patients, demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) with targeted agents; for instance, HER2-targeted therapies like trastuzumab and trastuzumab deruxtecan showed median OS improvements of 4-6 months in HER2-positive gastric cancer (ORR 47-50%), while anti-EGFR agents like cetuximab extended PFS by 2-3 months in KRAS wild-type colorectal cancer. VEGF inhibitors such as bevacizumab and ramucirumab yielded PFS benefits of 1.5-4 months across GI tumors, particularly in combination regimens. Emerging targets like CLDN18.2 with zolbetuximab achieved unprecedented median OS of 18 months in gastric cancer, and FGFR inhibitors like bemarituzumab improved OS in FGFR2b-overexpressing cases. However, resistance mechanisms, including secondary mutations and pathway crosstalk, were noted in 30-50% of cases, highlighting the need for ctDNA monitoring for adaptive therapy. Overall, targeted therapies matched to biomarkers via next-generation sequencing (NGS) or liquid biopsies resulted in a pooled hazard ratio (HR) for OS of 0.82 (95% CI 0.75-0.89) and PFS HR of 0.78 (95% CI 0.70-0.86), with adverse events primarily grade 1-2, though cardiotoxicity and hypertension occurred in 10-15%. These findings underscore the transformative potential of precision oncology in GI cancers, advocating for broader biomarker testing and combination strategies to overcome heterogeneity and resistance, ultimately paving the way for improved patient outcomes in this challenging disease spectrum.