Colon cancer treatments tailored to genes

Siteman Cancer Center researchers are customizing therapy for advanced colorectal cancer patients based on differences in their DNA.

The goals, according to lead researcher Howard McLeod, Pharm.D., associate professor of medicine, of genetics and of molecular biology and pharmacology, are to maximize the benefits of treatment and reduce the risk of a harmful reaction.

“We are using genetics to decide which therapy is best for a cancer patient,” McLeod said. “It’s not a new idea, but we finally have the technology to look at people’s DNA in a timely manner and adjust a patient’s therapy based on these insights.”

McLeod specializes in pharmacogenetics, which focuses on the interactions between medical treatments and genes. His study at Siteman is the first of its kind in the United States.

“Thanks to recent advances in science and technology, we now have a way of determining that therapy A may be dangerous for one patient but safe for another, or that a given patient might be more likely to have a positive response when treated with therapy B,” McLeod said.

He added that it’s really an example of multidisciplinary medicine at its best. “We could never do these studies if the radiation oncologists, the medical oncologists, the surgeons, the radiologists and the pathologists weren’t 100 percent on board,” McLeod said.

With support from the NIH, researchers in McLeod’s lab are also assembling an extensive list of genetic variations that can affect a patient’s response to colon cancer therapy.

To generate leads for genes that might potentially interact with colon cancer therapy, researchers first assemble a detailed list of key proteins known to interact with a drug. They then check if changes in genes that code for those proteins correlate with changed treatment outcomes.

Using data from the National Cancer Institute’s Clinical Trials Cooperative Group Program, McLeod followed up on potential pharmacogenetic links to colon cancer therapy already noted in earlier studies.

Early results from his group’s studies have confirmed a few genes that are clearly associated with either risk of severe toxicity or with the chance of a successful therapeutic response to treatment.

Citing a personal interest in colon cancer research, McLeod said he’s pleased colorectal cancer has a lead role in developing improved methods for fine-tuning treatments.

“Results from our studies of pharmacogenetic factors and colorectal cancer will help us think about how we can begin to apply the same techniques to other tumor types, including lung, breast and prostate cancers,” he said.

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