Jennifer Tovar, PharmD & Husna Rahim, PharmD
Genomic Warfare: Outsmarting Cancer Care with Pharmacogenomics. How can pharmacogenomics (PGx) maximize efficacy and minimize toxicity of cancer treatment? To outsmart cancer, PGx offers a genomic arsenal that enables clinicians to tailor chemotherapy and immunotherapy regimens based on a patient’s genetic profile. This approach tackles complexities in cancer pathology, drug resistance, and side effect management.
Somatic mutations drive therapeutic resistance. Cancer is now understood not just as uncontrolled cell growth but as a disease of the genome, driven by mutations that transform normal cells into malignant ones. Oncology PGx is unique from other PGx applications in that it examines both germline and somatic mutations, rather than germline mutations alone (Reizine & O’Donnell, 2022). Germline variations influence how the body processes drugs, guiding selection among alternative agents. In contrast, somatic mutations are specific to cancer cells and drive therapy resistance.
As cancer cell multiply, they create new mutations. One of the greatest challenges in oncology care is therapy resistance. As cancer cells multiply, they develop new mutations which combat or resist cancer treatment agents. For instance, secondary mutations in EGFR (e.g., T790M) or ALK rearrangements can render first-line therapies ineffective. By reassessing tumor genomics at progression, clinicians can detect resistance mechanisms and reorient therapy toward select alternative agents that exploit new vulnerabilities against these resistant clones (Calvo, et al. 2016). Integrating these layers of genomic insight supports durable therapeutic strategies, even in the face of resistance (Reizine & O’Donnell, 2022).
Genetic influence on symptom burden and pain management. Emerging evidence supports the clinical relevance of additional genes in influencing symptom burden and pain management in cancer care. For example, patients with DPYD gene variants experience reduced metabolism of fluoropyrimidines, increasing their risk of life-threatening adverse drug reactions (ADRs). Studies by Deneen et al. and Henricks et al. demonstrated that using CPIC/DPWG-endorsed genotypes to guide dose reductions significantly decreased severe toxicities in gastrointestinal and breast cancer patients (2016 & 2018, respectively). Validating these associations through rigorous studies could extend PGx benefits beyond cytotoxicity management into supportive and survivorship care.
Learn more about UGenome’s Personalized Medication Service, ProPEx, or contact UGenome. You can also find case studies for UGenome’s bioinformatics services Metabolite Identification, Bone Metastasis Risk Analysis in Breast Cancer, Survival Analysis with gene signatures in cancer
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