The Risks of Chemotherapy Enzyme Deficiency and the Importance of Genetic Testing

In 2025, a poignant case highlighted the critical need for genetic testing before administering certain chemotherapy drugs. JoEllen Zembruski-Ruple, a dedicated patient advocate in New York City, began treatment with capecitabine, a drug used to combat her squamous cell carcinoma. Despite its potential to prolong life, Zembruski-Ruple suffered severe adverse effects due to a genetic enzyme deficiency that prevented her body from safely metabolizing the medication.

Six days after starting treatment, she sought urgent care for mouth sores and swelling around her eyes. She was diagnosed with an oral yeast infection and discharged, but her condition worsened rapidly. She returned with severe diarrhea and vomiting, eventually deteriorating to the point where she could not swallow or speak. Her health declined further, leading to hospice care and her passing on March 25, 2025.

The underlying cause was a deficiency in the enzyme thymidine phosphorylase, essential for breaking down capecitabine. This deficiency, which about 1,300 Americans die from annually due to toxicity, can be identified through genetic testing. If discovered beforehand, doctors could adjust dosages or choose alternative treatments, preventing many deaths.

Despite the availability of such tests, routine screening remains rare in the U.S., partly due to high costs and lack of regulatory mandates. In contrast, European regulators have been urging testing since 2020, with the practice becoming more common.

Advocates emphasize that patients should have the right to decide whether to undergo testing, especially since genetic tests can now be performed quickly and affordably. Cases like Zembruski-Ruple’s underscore the importance of personalized medicine and the need for healthcare systems to prioritize genetic screening to avoid preventable tragedies. The medical community continues to evolve its approach, with recent guidance from authoritative panels suggesting more cautious use of chemotherapy drugs linked to genetic risk.

This story underscores the critical balance between effective cancer treatment and personalized risk assessment, advocating for increased awareness and routine testing to safeguard patients' lives.

Source: https://medicalxpress.com/news/2025-06-patients-chemo-survived-demanded-safe.html