What You Missed: The Expanding Role of Pharmacogenomics in Oncology
Pharmacogenomics (PGx) is quickly moving from “optional testing” to “recommended testing” in oncology—and recent regulatory shifts are accelerating that momentum. Updated FDA labeling and oncology guidelines now recommend testing for DPYD variants before starting patients on capecitabine or other fluorouracil-based therapies (like 5-FU), marking a significant step toward safer, more personalized treatment.
PGx testing empowers clinicians to identify patients at risk for severe—and sometimes fatal—drug toxicities before treatment even begins. By uncovering genetic variants that affect how patients metabolize commonly used oncology drugs, PGx provides critical insights that can directly inform therapy selection and dosing decisions.
The impact is already being felt across cancer care. In our recent webinar, “Personalizing Patient Care: The Expanding Role of Pharmacogenomics in Oncology,” experts explored how PGx testing is helping guide safer, more precise treatment strategies across a range of cancers, including colorectal, breast, gastric, pancreatic, and lung.
As the field continues to evolve, one thing is clear: integrating PGx into clinical workflows isn’t just an advancement—it’s becoming essential to delivering truly personalized cancer care.
Pharmacogenomics vs. Tumor Genomics
While tumor genomic profiling identifies somatic mutations within cancer cells that can guide targeted therapy selection, pharmacogenomics focuses on germline variants in certain pharmacogenes that influence how a patient metabolizes medications.
These inherited differences can determine whether a patient is likely to be a normal, intermediate, or poor metabolizer of certain drugs, which may significantly impact toxicity risk and dosing strategies.
Understanding this distinction is essential as oncology care continues to move toward more personalized treatment planning.
Why PGx Testing Matters in Oncology
Several commonly used chemotherapy agents rely on specific metabolic pathways. When these pathways are impaired due to genetic variants, patients may experience severe toxicity.
One well-known example involves the DPYD gene, which encodes the DPD enzyme responsible for metabolizing fluoropyrimidine-based chemotherapy drugs such as 5-fluorouracil (5-FU) and capecitabine.
Variants in DPYD can significantly reduce enzyme activity, allowing active drug to accumulate and increase the risk of serious toxicity.
Because of this risk, regulatory guidance has evolved to encourage or require testing for certain variants before initiating therapy with these agents.
Key Genes in Current Northstar PGx™ Testing
The webinar highlighted two clinically relevant pharmacogenes currently included in Northstar PGx testing:
DPYD
- Encodes the DPD enzyme and is responsible for fluoropyrimidine metabolism (e.g. 5-FU/fluorouracil, capecitabine)
- Common 5-FU-containing regimens used in CRC, breast, gastric and pancreatic cancers:
- FOLFOX
- FOLFIRI
UGT1A1
- Encodes the UGT1A1 enzyme and is responsible for clearance of the active metabolite of irinotecan
- Common irinotecan-containing regimens used in CRC, pancreatic, gastric and lung cancers:
- FOLFIRI
- FOLFIRINOX
Identifying these variants before treatment can help guide dose adjustments or therapy selection.
Integrating PGx Into the Oncology Workflow
PGx testing is most valuable when performed early in the treatment journey, ideally at diagnosis. This ensures clinicians have a patient’s metabolizer status available before they are prescribed therapies potentially affected by these pathways.
When integrated alongside comprehensive tumor profiling, PGx testing can provide a more complete picture of a patient's biology—supporting the best treatment decisions that balance efficacy and safety.
Watch the Webinar Recap
Want the full overview?
Watch the recap to hear the clinical discussion and learn how pharmacogenomics testing may support more informed treatment planning in oncology.