Optimising Systemic Therapy in Oncology: A Step Ahead in the Application of Pharmacogenetics, A Narrative Review
DOI:
https://doi.org/10.35516/jmj.v60i2.4269الكلمات المفتاحية:
Pharmacogenetics، Pharmacogenomics، Cancer، Chemotherapyالملخص
Elucidating the pharmacokinetics of anticancer agents is essential for optimising their safety and therapeutic efficacy. Pharmacogenetics and pharmacogenomics (PGx) provide a framework for understanding individual variability in drug response and minimising adverse effects by analysing genetic variants that affect drug-metabolising enzymes and membrane transporters. In oncology, where safety and efficacy are critical, personalised treatment guided by PGx markers and clinical recommendations is gaining increasing importance. Variants such as CYP3A4*14, *1, *18 and ABCB1 1236CC were associated with reduced imatinib efficacy and an elevated risk of toxicity. CYP2D6*17, *29, *4, *10, and *41 alleles were linked to diminished tamoxifen efficacy, while CYP2D6*17, *41, *10, and *5/*5 were reported in relation to various stages of relapse. Genotypes GSTP1 rs1695 c.313A>G (AG and GG), ABCC1(c.3173G>A and rs9332430), ABCB1 (c.1236C>T and 3435C>T), ABCC2 (–24C/T, rs2804398, and +9383C>G), as well as ABCC4 rs943288, were associated with increased toxicity from platinum-based therapies. Variants UGT1A1*28, *6 and UGT1A7 were implicated in irinotecan-related toxicity. Additionally, DPYD*2A (rs3918290), *13 (rs55886062), rs67376798, and HapB3 (rs75017182) were strongly associated with severe fluoropyrimidine-related toxicities and increased treatment-related mortality. As PGx research advances, its integration into routine oncology practice will be essential for optimising therapeutic outcomes and supporting a more individualised approach to cancer treatment.
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