Cancer Genomics: Targeting Treatment to the Patient

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Jeff Wigbels didn't smoke. He had no family history of cancer, and he was a triathlete and marathon runner. By many measures, he was a picture of health.

That was before October 11, 2006, when doctors discovered a baseball-sized tumor in his lung.

Wigbels, who is from Atlanta, had lung cancer, and further tests revealed that by the time it was detected, the malignant cells in his lung had metastasized to his chest, abdomen and brain. Facing a diagnosis of stage 4 lung cancer, Wigbels knew that the odds were heavily against his survival.

At the time, Wigbels's wife Tiffany was ready to give birth to the couple's second child. So Wigbels waited until a day after she delivered on Oct. 12 to tell her of his diagnosis -- and that he was unlikely to live long enough to see his child's first birthday.

"We held off telling Tiff until we had Jack," he said. "And the next day or two, right after that, I had to tell Tiff that quite frankly, there may not be an opportunity for me to be here to help raise our child, she may have to do that all by herself."

The initial treatment recommended to Wigbels was the standard regimen of radiation and chemotherapy. But after researching his options, Jeff met with Dr. Roy Herbst at the University of Texas M.D. Anderson Cancer Center. There, he enrolled in a clinical trial called BATTLE, designed to test the effectiveness of an individualized therapy based on tailoring treatments to the patient's genes.

Today he is alive, and he continues to defy the odds.

"The drugs were somewhat targeted for the most part to everything that was going on with me," Wigbels said. "It was not a random standard of care procedure."

Indeed, while all cancers are not equal, patients with cancer traditionally have been treated that way, with a standard treatment regimen built from chemotherapy, radiation and surgery.

But now promising breakthroughs in cancer research -- specifically in a field known as cancer genomics -- are giving doctors a new tool. Cancer genomics is a quest to understand what is wrong in that patient's genes and target treatment there. The patient's own genes are used to personalize treatment.

"The testing for the BATTLE trial helped determine which of four arms of the trial [Wigbels] would be assigned to," Herbst said, "and hence personalized his therapy."

Cancer Genomics: Targeting the Treatment to the Patient

Francis Collins, director of the National Institutes of Health, said the approach may prove to be a milestone in cancer treatment.

"It is the most exciting time in cancer research ever," Collins said. "Fifty years from now, people will look at how we treated cancer in 2010 and wonder how people went through that.

"My dream is that through cancer genomics we will discover in the coming years a long list of effective, targeted therapies that will take the place of what we do now for many patients and will lead to a circumstance where cancer is no longer such a feared diagnosis, but a chance to get a treatment that you know is going to work."

Cancer Genomics Researchers Seek Individualized Cancer Treatment

Even patients who have identical diagnoses may look completely different at the molecular level. Because of this, researchers are striving to develop ways to identify small-scale differences in cancer cells that would allow doctors to treat patients according to the genetic basis of their cancer.

"We're able to get out of that biopsy material the DNA and the RNA, the nucleic materials, so that we can look at the genes and the proteins to see what is wrong with that tumor, compare it to other tumors, and see if these genes are telling us which chemotherapy or which targeted therapy to use," said Dr. Harvey Pass, a cancer researcher at NYU Langone Medical Center who is also on the advisory board of Rosetta Genomics.

"This is the model of personalized cancer therapy," says Dr. Marc Ladanyi, chief of the Molecular Diagnostics Service at Memorial Sloan-Kettering Cancer Center in New York. "We don't just look at [a tumor] under the microscope to see how aggressive it is; we also characterize which mutations are present in the cancer, so that from the get-go you know if your cancer can be treated with specific drugs."

At Sloan-Kettering, patients with non-small cell lung cancer -- the most common form of the disease -- have their cancer cells tested for over 40 different mutations. Once a mutation is identified, doctors can suggest specific treatments based on the patient's cancer mutation.

Clinical trials are underway at the M.D. Anderson center to determine the success rate of genetic tests, such as the ones performed at Memorial Sloan-Kettering, not only in lung cancer but in metastatic colorectal cancer as well.

Cancer Genomics: Targeting the Treatment to the Patient

Currently, the most widely accepted genetic test used to guide cancer treatment is that for HER2, a mutation present in 15-20 percent of breast cancer patients. The HER2 test is now a standard recommendation for newly diagnosed breast cancer patients, because women with the HER2 subtype are more receptive to certain breast cancer therapies.

Genetic testing on tumor specimens, however, can be plagued by inaccuracy. So researchers at Johns Hopkins University in Baltimore are trying to take genetic testing to a new level. Rather than taking a closer look at the cancer cells, Dr. Bert Vogelstein and his colleagues there have developed a method that uses genomic sequencing to create blood tests. These tests, the said, could be used to monitor tumor levels after treatment and determine cancer recurrence.

"Using this approach, we can develop biomarkers for potentially any cancer patient," says Dr. Victor Velculescu, co-director of the cancer biology program at Johns Hopkins.

Such is the hope of Wigbels, who is now trying to make the treatments that have helped him more accessible to everyone. Following his experience, he founded TakeAimAtCancer.org to raise money for genomic cancer research.

For more on Wigbels's story, visit TakeAimAtCancer.org.

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