Pharmacogenomics in solid tumors: Integrating germline and somatic genetic variability for precision oncology

Background: Solid tumors exhibit substantial interindividual variability in therapeutic response and drug-related toxicity, which cannot be fully explained by clinical or tumor-specific factors alone. Pharmacogenomics has emerged as a critical component of precision oncology by elucidating how both germline and somatic genetic variability influence anticancer drug efficacy and safety.

Objective: This review provides a comprehensive and clinically oriented overview of pharmacogenomics in solid tumour’s, highlighting actionable gene–drug associations, translational relevance, implementation challenges, and emerging innovations shaping future oncology practice.

Methods: A narrative review of peer-reviewed literature published between 2020 and 2026 was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Human studies, systematic reviews, meta-analyses, and clinical guidelines focusing on pharmacogenomic biomarkers and gene–drug interactions in solid tumors were included.

Results: Germline variants in key drug-metabolizing enzymes, including CYP2D6, DPYD, and UGT1A1, significantly influence drug exposure, toxicity risk, and treatment outcomes across multiple solid tumors. Somatic alterations such as EGFR, KRAS, and BRCA1/2 mutations guide targeted therapy selection, resistance prediction, and tumor-agnostic treatment strategies. Despite robust evidence supporting pharmacogenomic-guided therapy, clinical implementation remains inconsistent due to infrastructural limitations, cost concerns, and gaps in clinician education.

Conclusion: Pharmacogenomics represents a foundational pillar of precision oncology by integrating host and tumor genetic information to optimize therapeutic decision-making. Advances in polygenic modeling, liquid biopsy technologies, artificial intelligence, and multi-omics integration are expected to accelerate clinical adoption. Systematic implementation of pharmacogenomics has the potential to improve treatment efficacy, reduce toxicity, and enhance patient outcomes in solid tumors.