Bittersweet Gene

Predicting drug response in colorectal cancer.

HEATHER L. VAN EPPS, PHD
PUBLISHED: 1:00 AM, TUE DECEMBER 9, 2008
Talk about this article with other patients, caregivers, and advocates in the Colorectal Cancer CURE discussion group.
On Easter Sunday in 2007, Doris Banks awoke from a nap with excruciating abdominal pain. Suspecting a burst appendix, she and her husband rushed to the emergency room. Her suspicion was confirmed, and Banks had an emergency appendectomy. But her surgery revealed something far more sinister than a ruptured appendix—Banks had colorectal cancer that had spread to her abdomen. The surgeon removed a large section of her colon and several lymph nodes along with her appendix.

Banks’ initial reaction was shock. “I had probably only missed five or six working days in my life,” she says. “I was just one of the healthiest people you would ever meet.”

Banks, a 53-year-old salon owner from North Carolina, was diagnosed with metastatic colon cancer; tests showed the cancer had spread to her liver. Over the next year, Banks received multiple rounds of chemotherapy and had a large portion of her liver removed.

After recovering from liver surgery, Banks faced more bad news. A CT scan in early 2008 revealed the cancer had continued to spread. “At that point, I was extremely discouraged,” recalls Banks, who had hoped the liver resection would remove the last of the cancer. “In your mind you think, ‘OK, this is going to get it, and then I’ll be on my way.’ ”

With standard treatment failing, Banks’ oncologist, Richard Goldberg, MD, director of oncology at the Lineberger Comprehensive Cancer Center at the University of North Carolina, considered putting Banks on a new cancer-fighting drug. But first he wanted to test her tumor for mutations in a gene known as KRAS, which, if positive, could mean she would have little chance of benefiting from the drug.

The drug Goldberg had in mind was Erbitux (cetuximab), which belongs to a growing family of targeted therapies that are changing the way doctors approach cancer treatment. By studying each patient’s tumor to determine which biological pathways have gone awry, oncologists can use targeted drugs to hone in on precisely those pathways. This tumor characterization strategy will also help doctors to pinpoint which patients are most likely—or least likely—to benefit from a given drug.

Erbitux and a related drug called Vectibix (panitumumab) both block a protein called EGFR (epidermal growth factor receptor), which promotes the growth and survival of tumor cells and is often expressed at high levels on colorectal tumors.

In patients such as Banks who have advanced disease and do not respond to standard chemotherapy, Vectibix and Erbitux can be beneficial. Recent studies have shown that both drugs, given alone or in combination with standard chemotherapy, can improve response rates and progression-free survival in these patients. Despite the benefit of these drugs, however, the five-year survival rate for patients with stage 4 disease still hovers at a discouraging 5 to 10 percent.

The likelihood of benefiting from EGFR inhibitors is not equal among all patients. Erbitux and Vectibix were initially approved in 2004 and 2006, respectively, for the roughly 75 percent of colorectal cancer patients whose tumors express EGFR. And, in some studies, higher than normal expression of the receptor was linked to an even better response.

Talk about this article with other patients, caregivers, and advocates in the Colorectal Cancer CURE discussion group.
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