Patients and families turn to genomic medicine to treat cancer
Most of us probably associate being sick with the entire body- a fever, aches, chills and other broad symptoms. When it comes to a disease like cancer, we might take an organizational step or two down to think of a specific organ or tissue: breast, lung or brain cancer.
But increasingly, patient’s stories point clearly toward a finer resolution of cancer diagnosis, down to the level of a single gene. A report in the New York Times last week describes how a team of researchers worked to identify the genetic aberration underlying a colleague’s cancer, and helped treat his leukemia with an off-label drug currently used to treat kidney cancers.
Dr. Wartman’s success story highlights an increasingly dominant view of cancer- not as a single disease, nor as a disease of a particular tissue or organ, but a constellation of mutations unique to a cancer cell. The genetic changes that cause one patient’s leukemia may be completely different from those underlying another patient’s cancer. And some of these mutations may bear greater resemblance to renal or lung tumors than to any kinds of leukemia.
Knowing precisely which mutations drive a patient’s tumor, physicians can potentially choose a therapy targeting a precise genetic aberration rather than resorting to a generic chemotherapeutic regimen for leukemia. But questions of how to identify these mutations and who pays for them abound.
As a cancer researcher himself, Dr. Wartman was particularly fortunate with access to the latest research. His colleagues at Washington University included him in a research study, with the instruments, resources and manpower to sequence his entire genome and analyze changes in gene expression to find one potential genetic driver, an over-expression of the FLT3 gene. Increased expression of FLT3 is linked to cell growth and proliferation in many forms of leukemia and other cancers, and one drug on the market, Sunitinib (Pfizer), targets FLT3 over-expression in advanced kidney cancers.
When his insurance company refused to cover his off-label use of the drug and Pfizer turned him down from their compassionate care program, he used his own funds to cover the cost of a week’s medication (at the rate of $ 330 each day). His colleagues chipped in to cover another month of treatment.
After the treatments, multiple tests show his bone marrow free of cancer cells. Time will tell whether the month-long treatment was fully effective. For now, Dr. Wartman and his colleagues are planning a clinical trial to test the success of Sunitinib in treating FLT3-overexpressing leukemia in other patients.
His story highlights both the price and the value of such genetic gambles in cancer treatment. Pending clear direction from insurance companies and healthcare providers, accessing the technology and researchers who can identify genetic aberrations in cancers remains restricted to a small fraction of patients with the means to reach these scientists.
The effectiveness of molecular-targeted medicines for long-term remission is still being understood. In some cases, patients may respond remarkably well to such drugs initially, only to have their cancer rebound within a few months. Two studies in Nature this week suggest that one reason for this recurrence may be in the tissues surrounding tumors rather than the tumors themselves. Secondary mutations that evolve in tumors over time could also contribute to cancer recurrence and drug resistance evolved over treatment. Most of all, only a handful of the mutations known to drive different cancers can be effectively targeted by molecular therapies. As of 2011, less than 100 drugs had approved genetic indications.
Several translational research initiatives are attempting multi-pronged approaches to address these concerns. Collaborations between academic researchers and pharmaceutical developers hope to integrate tumor biology research with drug development processes to speed up the process of identifying the best molecular therapeutics for specific mutations. While drug manufacturers frequently form academic collaborations with laboratories studying the basic genetic pathways underlying cancer progression, a recent NIH initiative also offers academics the opportunity to find new uses for ‘abandoned’ pipeline molecules.
Collectively, these researchers seem clearly set to target cancer not as a disease of a tissue or organ system, but a disorder of the genes. Efforts by Dr. Wartman’s colleagues and other scientists hope to establish a roadmap of cancer genomics, complete with pathways, genetic drivers, tumor markers and the drugs that target them with increasing precision.
As Dr. Ley, Director of the Washington University genome center, phrases it in the recent New York Times article, “For the past 40 years, we have been sending generals into battle without a map of the battlefield. What we are doing now is building the map.”