Doctors know patients sometimes respond very differently to the same drug. St. Jude Children’s Research Hospital is a leader in studying how differences in the makeup of the genes inherited from each parent influence how patients react to certain drugs. St. Jude is also a pioneer in using the information to guide clinical care.
An international research team led by St. Jude scientists has discovered how such inherited differences can cause serious problems during leukemia treatment.
The scientists showed that patients who inherit certain versions of a gene named NUDT15 were more sensitive to an important family of anti-cancer drugs. The drugs, called thiopurines, cause serious side effects in these patients.
Researchers discovered that is because the patients were less able to break down the drugs. This, in turn, increased the risk that the drug would build up in the patients’ bodies.
The findings also helped explain why Asian and Hispanic patients often cannot tolerate thiopurines at standard doses. Researchers found that the high-risk versions of the gene are more common in people across Asia and those of Hispanic ancestry.
“The results suggest that in the future we can improve the safety and effectiveness of chemotherapy by screening patients for the high-risk versions of the gene and using the information to adjust the dose of the drug,” said Jun J. Yang, PhD, of the St. Jude Department of Pharmaceutical Sciences.
The research was published in the journal Nature Genetics.