INTEGRATING GERMLINE TRANSPORTER PHARMACOGENOMICS AND SOMATIC MUTATIONS IN CANCER THERAPY
DOI:
https://doi.org/10.36074/grail-of-science.20.02.2026.164Keywords:
Germline variants, Somatic variants, Pharmacogenetics, Cancer therapySummary
This review examines the critical role of genetic variation, including both germline and somatic mutations, in shaping cancer therapy outcomes. Using population-based data from 185 countries, it highlights the growing global burden of cancer, projecting a threefold increase in incidence and mortality in low-Human Development Index (HDI) countries by 2050, while high-HDI countries are expected to experience smaller increases. Lung cancer is identified as the leading cause of cancer incidence and death and is projected to remain so, accounting for over 10% of cases and fatalities. The study emphasizes the significance of drug transporter genes, particularly those in the ATP-binding cassette (ABC) families, in regulating drug absorption, distribution, metabolism, and excretion, thereby influencing both efficacy and toxicity. Clinical evidence demonstrates that polymorphisms in ABCB1, ABCC1, ABCC2, and ABCG2 affect patient responses to targeted therapies, such as osimertinib and abemaciclib, as well as conventional chemotherapy. Somatic variants, including the BCR-ABL fusion in chronic myeloid leukemia and mutations in EGFR, ALK, BRAF, and MEK, play a central role in tumor progression, drug resistance, and therapy sensitivity, underscoring their relevance in precision oncology. The review advocates integrating both germline and somatic pharmacogenomic testing into routine clinical workflows, developing evidence-based guidelines for actionable variants, and implementing decision-support tools for interpreting complex genetic data. It highlights the need for diverse population studies to ensure global applicability. Advanced molecular approaches, including circulating tumor DNA and liquid biopsies, are recommended for dynamic tumor monitoring and adaptive therapy planning. Together, these strategies aim to optimize personalized cancer treatment, improve therapeutic outcomes, minimize adverse effects, and support the broader adoption of pharmacogenomic-guided oncology.
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Copyright (c) 2026 Parchami Ghazaee Sepideh, Kateryna Marchenko-Tolsta, Iryna Tymchenko, Oke Temitope
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