Study links chemotherapy response to heritable factors

Findings guide future research on chemotherapy resistance

Study links chemotherapy response to heritable factors
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Howard McLeod, PharmD, is the project's principal investigator.

Media contact: Ellen de Graffenreid, 919-962-3405, edegraff@med.unc.edu

Thursday, Oct. 27, 2011

CHAPEL HILL, N.C. – Physicians and scientists know that a patient’s genetic makeup can affect how well a particular drug works for them.  Recent findings in pharmacogenomics are enabling safer use of drugs like the anticoagulant warfarin, with fewer side effects for patients.  However, the role that genetics plays in the patient response to common chemotherapy drugs had not been evaluated.

A new study from UNC Lineberger Comprehensive Cancer Center and UNC’s Institute for Pharmacogenomics & Individualized Therapy evaluated 29 commonly used cancer chemotherapy drugs in the laboratory and found that the influence of genetics on chemotherapy response varies widely between different drugs and different classes of drugs.

The study was published online in the journal Pharmacogenomics.

“"We know that chemotherapy works to kill cancer cells, but the problem is that we don’t know exactly why it works better for some patients than for others,” said project researcher Kristy Richards, MD, PhD, who is a member of UNC Lineberger Comprehensive Cancer Center.

The team tested inheritance of chemotherapy drug effect by using cancer cells derived from 14 extended families.  Response varied a great deal among the 29 tested drugs.  Genetics influenced as little as 15 percent of response to some drugs and as much as 60 percent for others.  

The team also found genetic markers that were unique to drugs from the same chemical family.

“Our results can help us and other scientists ‘zoom in’ on the region of the genome that holds clues to why chemotherapy – or certain drug classes of chemotherapy – doesn’t work as well for some people,” said Howard McLeod, PharmD, the project’s principal investigator, Eshelman distinguished professor in the UNC Eshelman School of Pharmacy and a member of UNC Lineberger Comprehensive Cancer Center.

Other researchers include Institute members Eric Peters, Alison Motsinger-Reif, Tammy Havener, Lorraine Everitt, Venita Watson, Michael Wagner and Kristy Richards, who is also a member of UNC Lineberger, as well as Nicholas Hardison from the UNC Bioinformatics Research Center and Mike Province from Washington University in St. Louis.

The project was supported by the NIH Pharmacogenetics Research Network, the National Institute of Environmental Health Sciences, the University Cancer Research Fund and Triad Golfers Against Cancer.

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