In the first of three New York Times front-page articles on how genomics may affect cancer treatment in the future, Gina Kolata, one of our premier science and health writers, described the story of Dr. Lukas Wartman. During his final year of medical school in 2002, Dr. Wartman was diagnosed with acute lymphoblastic leukemia. Following nine months of intensive chemotherapy and 15 months of maintenance chemotherapy, he went into remission. Five years later, when the cancer returned, he underwent the more risky remedy of intensive chemotherapy followed by bone marrow transplantation from his younger brother. His prognosis at that time: 4-5% survival in patients who have relapsed with his form of leukemia.
Yet, he stayed in remission for three years, when his cancer returned a second time. His doctors tried new chemo and hormonal therapies to no avail.
It happens that Dr. Wartman works at the Washington University’s Genome Institute, and his colleagues decided to try a radical solution. They anticipated that fully sequencing the genes of his tumor, and healthy cells for comparison, would be difficult to interpret because the number of genetic mutations in his cancer would be very high. So, they also analyzed his RNA, a close chemical cousin to DNA, to see what proteins his tumor genes were producing. They found one gene in overdrive, making huge amounts of a tumor growth factor called FLT3. Better yet, a drug already on the market for kidney cancer targeted the FLT3 receptor and could be prescribed off label.
To make a long story short, this is a success story. He gained access to the drug and is now again in remission.
There are many lessons in this story that I want to share with you:
1) The genes that drive a cancer may be much more significant than the tissue or organ of origin. “One woman’s breast cancer may have different genetic drivers from another woman’s and, in fact, may have more in common with prostate cancer in a man or another patients lung cancer”, writes Ms. Kolata.
2) A cocktail of medicines targeting several key aberrant genes at once may represent the future of chemotherapy. “Until you know what is driving a patient’s cancer, you really don’t have any chance of getting it right. For the past 40 years, we have been sending generals into battle without a map of the battlefield”, writes Dr. Ley, the director of the genome institute.
3) The intensive analysis of this patient’s genome took months and lots of resources provided by the University. It is not scalable at this time.
4) Leading cancer researchers are starting companies to find genes that might be causing an individual’s cancer to grow, and the whole pharmaceutical industry is now very interested in this approach.
5) I believe the earliest this type of an approach may have wider applicability and be affordable is 15-20 years.
The article by Gina Kolata described above showed how, in the future, we will be treating some patients with breast and colon cancer, with therapies approved for lung cancer or leukemia. Individualization of gene and protein expression will dictate the treatment, not the organ of origin of the tumor.
So, what does a patient with cancer do now? The cancer treatment terrain is changing rapidly. One should seek second opinions and counseling whenever possible, should ask whether your medical center has a tumor registry, so that a portion of your tumor can be frozen and held for future genomics and other testing.
One approach researched and used by Dr. Daniel Dunphy at Anatara is the use of a blood-based test, which identifies and isolates circulating tumor cells or CTC’s. Gene expression profiles of these CTC’s are then profiled against multiple chemo and natural therapies to determine what the CTC’s are sensitive or resistant to. A similar approach of matching a sample to a battery of potential treatments is used routinely in choosing which antibiotic to use against a given bacterial infection.