SEP 25, 2019 6:50 AM PDT

How does a drug for colorectal cancer work?

WRITTEN BY: Nouran Amin

Colorectal cancer is a fatal and common disease, and treatment decisions are often based on what genes have been mutated in the development of the cancer. This means that certain patients with colorectal cancer may benefit from the chemotherapeutic ‘cetuximab’ while other patients may be unresponsive. However, the mechanism of how cetuximab works in those patients that do respond to treatment remains largely unknown--that is until a recent study published in the journal Science Signaling.

"This study has direct clinical implications because now doctors can start prescribing this effective drug to colorectal cancer patients with this mutation immediately," says Edward Stites, senior author of the paper and an assistant professor in the Integrative Biology Laboratory. "The work also highlights the necessity of mathematical models based on fundamental biochemistry as a tool for understanding the behaviors of biological networks that are relevant to disease."

For the first time, researchers have used experiential data with computational biology to detect the mechanism of how colorectal cancer patients respond to the therapeutic. 40 percent of colorectal have a mutated KRAS gene that results in unresponsiveness to cetuximab. But, patients with the KRAS G13D mutation have been the exception and successfully respond to treatment with cetuximab.

"Our goal was to elucidate a mechanism for why tumors that harbor KRAS G13D mutations are sensitive to cetuximab," says Thomas McFall, first author on the paper and a postdoctoral fellow in the Stites lab. "Understanding this mechanism will aid doctors in receiving insurance support for prescribing cetuximab, which could benefit upwards of 10,000 colorectal cancer patients per year."

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"This work demonstrates the power of computational systems biology approaches to address problems in personalized medicine," says Stites. "Doctors could sequence the gene to find out if the patient has this KRAS G13D variant, and if they do, then doctors could confidently prescribe cetuximab. That's important, because it will give many cancer patients a new treatment option."

Source: Salk Institute

About the Author
Doctorate (PhD)
Nouran is a scientist, educator, and life-long learner with a passion for making science more communicable. When not busy in the lab isolating blood macrophages, she enjoys writing on various STEM topics.
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