Powers of Prediction

Predictive markers help oncologists match patients with the most effective treatments. 

When Troy Richards was diagnosed in 1999 with a rare cancer of the adrenal glands called adrenocortical carcinoma, or ACC, his treatment options were either surgery or a drug called Lysodren (mitotane), a decades-old agent associated with severe side effects. The 44-year-old Scottsdale businessman opted for surgery, but in 2004, the cancer showed up in his left lung and then in his liver six months later.

After surgeries to remove the tumors, Richards had a molecular profile to identify any unique attributes contained within the genetic signature of his cancer. Based on the results, Richards and his oncologists were able to locate a target for attack.

“I think of a molecular profile as an educated review of the tumor’s genetics. My molecular profile identified several targets,” says Richards, who was so impressed with the promise of targeted genetic research that he initiated the ATAC Research Project (www.atacfund.org) to rapidly advance new treatments for ACC.

“We decided to go after one target in particular—an up-regulated gene that is highly expressed in multiple myeloma,” says Richards. Even though he didn’t have multiple myeloma, he received 21 treatments of the multiple myeloma drug Velcade (bortezomib). “I am now coming up on two years in remission.”

Examining a patient’s tumor for predictive markers allows oncologists to know ahead of time whether the tumor is likely to respond to the therapy being considered. Even among patients with the same type of cancer, responses can vary considerably, not only in terms of the drug’s impact on the tumor, but also in terms of the severity of side effects experienced by a patient.

The one-drug-heals-all approach is falling to the wayside as a person’s genetic information foretells which medical therapy has the greatest odds for benefit. Although they’re not yet widely available and the results aren’t foolproof, predictive markers—a class of biomarkers—can be used to match patients with therapies that are more likely to be effective with potentially fewer side effects, or rule out drugs that won’t be effective.

“In cancer genetics, researchers study mutations in the tumor to figure out what caused the tumor in the first place,” says Carl Yamashiro, PhD, a senior researcher at the Biodesign Institute at Arizona State University. “In contrast, human genetics usually deals with inherited mutations that are passed down from generation to generation, or mutations that give a person an increased predisposition to developing a disease.”

New technology allowed researchers the ability to analyze multiple gene interactions and multiple gene pathways to develop cancer genetic tests. Understanding the interplay between numerous genes and their associated proteins increases the accuracy of predictive marker tests.

“The molecular profile gave me a better idea of what genetic pathways are causing my cancer to spread,” says Richards. “It gave me a little more hope that we may be able to try something that no one had ever tried on ACC.” 

The challenge, says Yamashiro, is to develop drugs that kill the tumor without harming the patient. “The idea is to develop more targeted therapies to reduce toxicity to the body, while saving a patient from unnecessary side effects,” says Yamashiro. 

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