Like many oncologists, Eric P. Lester, M.D., was faced with a dilemma: seven patients with advanced, incurable cancer, an arsenal of drugs that may or may not help them, and not enough solid proof about treatment efficacy to guide him.
So Dr. Lester devised what he called a “simple-minded experiment” that illustrates the promise of personalized medicine. Using DNA microarray “chips,” Dr. Lester analyzed his patients' tumors for expression of genes associated with good response to various anti-cancer drugs, and based his drug treatment plans on the results. Four out of seven patients with advanced cancer enrolled in the extremely limited study had a better outcome than expected.
The finding, presented today in Atlanta, Ga. at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development, shows that “a personalized molecular oncology approach, basing chemotherapy on relative gene expression in tumors, holds promise even at the relatively crude level employed here,” said study investigator, Dr. Lester, president of Oncology Care Associates in St. Joseph, Mich.
To obtain and analyze chip data, Dr. Lester worked with Craig Webb, Ph.D., Director of Translational Medicine at the Van Andel Research Institute in Grand Rapids, Mich.
The study is unusual because oncologists don't yet base most of their treatment decisions on gene profiling, especially when it might involve pairing drugs together in a novel combination or using varied doses, Dr. Lester said. “Much of clinical medicine is an educated guess, and this was an attempt to come up with a better approach by using the technology of a gene chip to make multiple, highly educated guesses simultaneously,” Dr. Lester said.
Dr. Lester added that one of the seven participating patients died before the gene chip was used to direct therapy.
Many current clinical trials involving gene expression examine effectiveness markers for individual drugs rather than combinations of drugs or different doses of agents used together for the first time. To truly help the most patients, Dr. Lester said, all potentially effective drugs and combinations must be matched up against the unique genetic profile of a patient's tumor, he said.
“Effective cancer treatment depends on understanding the biology driving the cancer, but because each tumor is different, it is very hard to personalize care and do a rigorous scientific experiment at the same time.”