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Q: Tell us about your work and what drew you to PGx.

I’m Becky Winslow, PharmD, founder and president of inGENEious RX Inc. My work focuses on helping diagnostic innovators bring pharmacogenomic and molecular testing into routine clinical care. In my former work as a pharmacist, I saw how much medication response can vary from patient to patient. That experience drives my interest in practical, clinically useful PGx that helps care teams make more informed treatment decisions.

Q: Why does germline PGx matter in oncology?

Precision oncology often focuses on the tumor: What mutations are present? Which targeted therapy may work? Germline PGx asks a different, complementary question: How might this patient’s inherited genetics affect medication response?

That matters because cancer care often involves powerful therapies, narrow dosing windows, and multiple supportive-care medications. PGx can help clinicians identify patients who may be at higher risk for serious toxicity, altered drug exposure, or avoidable treatment disruption before problems occur.

Q: How does the framework support implementation?

The framework helps institutions prioritize and deploy PGx results according to urgency, actionability, and workflow needs. Not every result warrants the same operational response. Some gene–drug pairs require clear action before treatment begins; others require clinical context, local protocols, or shared decision-making. A tiered approach helps oncology programs align evidence strength, allele interpretation, clinical consequence, feasibility, EHR/CDS strategy, and governance from the outset.

Q: What belongs in Tier 1?

Tier 1 includes safety-critical gene–drug pairs where missing an actionable result could lead to early, serious, and potentially preventable toxicity. Patients with DPYD intermediate or poor metabolizer phenotypes are at increased risk of severe, or even fatal, fluoropyrimidine toxicity with standard dosing,^1,3 while patients with TPMT or NUDT15 intermediate or poor metabolizer phenotypes are at increased risk of severe thiopurine-related myelosuppression, especially when reduced-function phenotypes are present in both genes.²

Because these consequences can occur early and may be preventable with prescribing changes, results must be clearly interpreted, available before prescribing, and connected to the prescribing workflow so the care team knows what action to consider.

Q: How does PGx support care beyond chemotherapy?

Tier 2 is appropriate for strongly supported PGx pairs whose consequences are typically less immediate and more manageable through dose adjustment, monitoring, medication selection, or follow-up. CYP2D6 and tamoxifen is one example: reduced CYP2D6 activity can lower endoxifen exposure, so clinicians may consider alternative endocrine strategies based on the broader clinical picture. Tier 2 also includes supportive-care medications for pain, nausea, depression, inflammation, seizures, and other oncology needs, where advisory or longitudinal CDS can support symptom control, tolerability, adherence, and treatment continuity.

Q: What should programs know about Tier 3?

Tier 3 includes PGx associations with regulatory recognition but less standardized implementation pathways. UGT1A1 and irinotecan is one example: FDA labeling recommends considering UGT1A1 testing and starting-dose reduction for known poor metabolizers because of increased neutropenia risk.⁴ Because no CPIC prescribing guideline exists, institutions must define phenotype-based dosing, escalation, documentation, clinician guidance, and governance before routine deployment.

Q: What is the most practical way to begin?

Start where the evidence is strong, the clinical consequence is serious and time-sensitive, and the prescribing action is clear. Then build the infrastructure around those results: allele coverage, genotype-to-phenotype translation, report language, EHR alerts, clinician education, and multidisciplinary governance. PGx should not replace clinical judgment, monitoring, or shared decision-making; it should make those decisions better informed. Used responsibly, oncology PGx can help precision medicine look beyond tumor biology and account for the individual patient receiving treatment.

References

1. Amstutz U, Henricks LM, Offer SM, Barbarino J, Schellens JHM, Swen JJ, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update. Clin Pharmacol Ther. 2018;103(2):210-216. doi:10.1002/cpt.911
2. Relling MV, Schwab M, Whirl-Carrillo M, Suarez-Kurtz G, Pui CH, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. Clin Pharmacol Ther. 2019;105(5):1095-1105. doi:10.1002/cpt.1304
3. Sharma BB, Rai K, Blunt H, Zhao W, Tosteson TD, Brooks GA. Pathogenic DPYD variants and treatment-related mortality in patients receiving fluoropyrimidine chemotherapy: a systematic review and meta-analysis. Oncologist. 2021;26(12):1008-1016. doi:10.1002/onco.13967
4. Pfizer Labs. CAMPTOSAR (irinotecan hydrochloride) injection, for intravenous use: prescribing information. U.S. Food and Drug Administration; 2024.

For the full tiered framework and implementation details, visit thermofisher.com/pgxeducation-oncology.

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