Genetic Testing Enhances Safety and Efficacy of Chemotherapy in Gastrointestinal Cancer Patients
Genetic testing for DPYD and UGT1A1 variants can significantly reduce severe side effects of chemotherapy in gastrointestinal cancer patients, advancing personalized treatment strategies.
Recent research highlights the significant benefits of genetic testing in managing chemotherapy for gastrointestinal (GI) cancers, such as colorectal and pancreatic cancers. Chemotherapy, a common treatment for these cancers, can cause severe and, at times, life-threatening side effects in patients carrying specific genetic variants that affect drug metabolism.
A groundbreaking study conducted by the Perelman School of Medicine at the University of Pennsylvania involved 517 GI cancer patients scheduled to undergo chemotherapy with drugs like fluoropyrimidines and irinotecan. Patients were divided into two groups: 288 individuals received blood tests to identify genetic variants in the DPYD and UGT1A1 genes, which influence how these drugs are processed in the body.
The findings showed that patients with identified genetic variants who received tailored dose reductions experienced significantly fewer severe side effects—38% compared to 65% in those who received standard doses without genetic testing. Additionally, the genetically tested group was less likely to require dose adjustments or treatment discontinuation, demonstrating improved safety and treatment adherence.
The DPYD gene produces an enzyme critical for breaking down fluoropyrimidines. Variants in DPYD can impair this process, leading to drug accumulation and toxicity. Similarly, variants in UGT1A1 affect the processing of irinotecan, increasing the risk of diarrhea and white blood cell reduction. Identifying these variants allows physicians to personalize chemotherapy doses, reducing harmful effects while maintaining treatment effectiveness.
Lead researcher Sony Tuteja emphasized the importance of integrating genetic testing into clinical practice, noting that it is both feasible and vital for patient safety. She explained that rapid testing results—available in about a week—can help guide safer treatment decisions, potentially preventing up to 1,300 deaths annually in the U.S. due to chemotherapy side effects.
Current standard protocols often overlook genetic differences, which can compromise patient safety and treatment outcomes. This study underscores the move toward precision medicine, where tailoring therapy based on genetic profiles can optimize efficacy and minimize risks for GI cancer patients.
Source: https://medicalxpress.com/news/2025-08-genetic-chemotherapy-gastrointestinal-cancer-patients.html
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