Imagine a world in which cancer isn't diagnosed according to where it is found on the body but according to genes found in the tumor itself. Patients with skin cancer, colon cancer and parathyroid cancer, for example, might be reclassified as "B-Raf mutation" patients and be treated with the same mutation-specific drugs. Instead of receiving breast cancer-specific chemotherapy, a breast cancer patient might join those with ovarian, uterine and cervical cancer to receive drugs targeted at inhibiting the PIK3CA mutation found in their tumors.
This paradigm shift may seem revolutionary, but more than a thousand patients have already been treated this way by researchers at MD Anderson Cancer Center in Houston.
In the largest study of its kind, researchers enrolled more than 1,150 cancer patients in phase I clinical trials to test the effectiveness of genetically targeted drug therapies -- an approach known broadly as personalized medicine. The results of these clinical trials will be presented today at the American Society for Clinical Oncology conference in Chicago.
The trial patients have bladder, breast, cervical, colorectal, gastric, liver, lymphoma, lung, melanoma, ovarian or any number of other cancers, but cancer location didn't necessarily determine their treatment. Patients were treated according to which of 12 known genetic mutations researchers found in their tumors. For instance, a patient in a trial for the PIK3CA mutation might include those with ovarian, cervical, uterine or breast cancer.
In a world used to dividing up cancers by body part and assigning colored ribbons accordingly, the gene approach to treatment marks a fundamental change in the way we even think about cancer.
"We classify cancers according to where they start, but each cancer is probably many types of cancer. The bigger picture is what are the genetic abnormalities that make that cancer grow. We've known about these mutations for a long time, but it's only recently that we have new drugs to target [them]," says Dr. Gerald Falchook, assistant professor in the department of investigational cancer therapeutics at MD Anderson.
The concept of genetically personalized cancer treatment has been a goal among cancer researchers for years, but the MD Anderson trial offers hope that widespread use of these kinds of treatments are within reach.
"Traditional treatments for cancer, such as chemotherapy, are one size fits all. All lung cancer patients might receive the same type of chemotherapy," says Falchook. While this approach can be effective, it ravages the patient's body by attacking all of a patient's cells in hopes of killing the cancer.
Genetically targeted therapy, on the other hand, isolates the abnormal proteins within the cell that only occur in the cancerous tumor itself. "This has led to the development of drugs that are less toxic than traditional chemotherapy," he says. And for patients with identifiable genetic mutations, this type of treatment can be effective when nothing else has worked.
Last Resort Results in De Facto Cure
For Casey Carleton, 32, of Bartelsville, Okla., four traditional treatments, including chemo, radiation and surgery, had failed to stop the progression of his melanoma, which had spread from his skin to his lungs in 2008. He was given a 35 percent chance of living to see 2010.
As a "last resort," Carleton signed up for the MD Anderson trial in January 2010, where his cancer was treated not specifically as melanoma but as a "B-Raf" mutation cancer. He received an experimental drug that might also be taken by other B-Raf patients with colon cancer or parathyroid cancer. Unlike the harrowing chemo and surgery he had undergone in the past two years, his tailored treatment consisted of two pills, three times a day. Within two weeks, the remaining tumor in his lung had shrunk by 50 percent. At 16 weeks, he was officially in remission.
"It was such a relief. I didn't know if I was going to see my youngest son's first birthday, and now he's three. I get to keep going, coach softball, be with my kids," Carleton says. "For me, so far, this is a cure for my melanoma."
Carelton's wife Mary Ann is a little more cautious about the outcome: "Every nine weeks he goes in for scans to make sure it's still working. We call it 'scanziety' whenever those trips come up. For now, we live our lives nine weeks at a time and hope that he's one of the lucky ones that are cured for life."
The MD Anderson trial is part of a general movement toward personalized, genetically based cancer treatment. Over the course of the past few years, a number of studies have investigated the advantages of treating cancer according to genes instead of according to site.
In 2009, Massachusetts General Hospital began one of the most ambitious programs in personalized medicine when they sought to map the genetic fingerprint of the tumors of nearly all new cancer patients. They tracked 110 genetic abnormalities on the 13 major cancer genes, and used this information to tailor-make treatment cocktails, ideally avoiding the expensive, side effect-laden hit-or-miss approach that had been the standard of cancer care for decades.
The MD Anderson program takes this approach a step further by testing new genetically targeted drug therapies in a clinical trial environment. Though the results so far are more "proof of principle rather than proof itself," says Dr. Len Lichtenfeld, deputy chief medical officer at the American Cancer Society, the findings are nonetheless promising.
This is "the future" of cancer care, says Dr. Stefan Gluck, clinical director of the Braman Family Breast Cancer Institute at the University of Miami.
The trials' positive results come with several caveats, however. Not every cancerous tumor has an identifiable mutation that would make such a targeted approach possible. Within the trial published today, of the 852 patients enrolled, only 354 had one or more actionable gene mutations.
Carleton's case highlights the miraculous results that can occur when just the right drug is matched to just the right patient. While this is the ultimate goal of personalized medicine, the science isn't quite there yet.
For instance, only half of melanoma patients have the B-Raf mutation, and even among those who do, some don't respond as well to the drugs as Carleton because their cancers might consist of a dozen other unknown genetic mutations.
To put it in perspective, all of the patients in the MD Anderson trials were in a similar situation to Carleton: Multiple traditional cancer therapies had failed and they were at the end of their rope. When treated with drugs targeted to their specific genetic abnormalities, about one in three had a good response. For patients with those abnormalities who received traditional treatment, only one in 20 had a good response.
Even for those who qualify for this approach, "most advanced cancers still don't respond probably due to the presence of multiple genetic abnormalities that contribute to resistance to the treatment given," says Dr. Richard Schilsky, deputy director of the Comprehensive Cancer Center at the University of Chicago. "That said, the approach is much more promising than just pulling something off the shelf for a patient with advanced cancer."