June 2, 2005
Gene Signature Could Revolutionize Cancer Care
Discovery should help doctors tailor treatment to specific tumor type
Scientists have identified an 11-gene "signature" in cancer tumors that appears to predict prognosis in at least 10 types of malignancies.
If it passes further testing, the signature may help doctors and patients decide on therapies that suit particular cancer types, a giant step forward in the emerging era of tailored treatments.
"It's a very exciting study," said Dr. Jay Brooks, chairman of hematology/oncology at the Ochsner Clinic Foundation in New Orleans. "It's using molecular genetics to try to predict which patients will respond or won't respond to current therapies. Then we would be able to offer patients who may have a particularly resistant type of a cancer other therapeutic options."
"It will allow each individual to predict with 95 percent or greater accuracy what would be the likelihood of successful therapy," added study author Dr. Gennadi Glinsky, an associate professor of molecular genetics and cancer biology at Sidney Kimmel Cancer Center in San Diego.
"If your cancer can be cured with just surgery alone, then you just go on and take it and have a great deal of expectation for a happy life," Glinsky explained. "If your disease profile belongs to the 30 percent that will fail therapy, you will know this well in advance and be able to choose advanced treatment or even novel therapy. We will be able to focus on those who need our focus and let those patients who will be cured with existing therapy go on with their lives."
The findings appear in the June 1 issue of the Journal of Clinical Investigation.
The study was based on the relatively new concept that tumors contain a certain proportion of stem cell-like cells along with other cells. These cells, it is hypothesized, are responsible for tumor progression and spread. The BMI-1 pathway in which the cells are activated could provide crucial information about the tumor.
The researchers identified the genetic signature in a mouse cancer model, as well as in tumors from human prostate cancer patients.
They then looked at the prognostic power of this signature in more than 1,000 individuals diagnosed with several different types of cancer: prostate, breast, lung, ovarian, bladder, lymphoma, mesothelioma, acute myeloid leukemia and two types of brain tumors.
When this signature was present in primary tumors, patients experienced a shorter time to disease recurrence, and were also more likely to experience cancer spread and to die after being treated.
The findings also seemed to bolster the idea that a tumor's potential to spread is determined relatively early in the course of the malignancy.
At the very least, the authors of an accompanying commentary state, the signature may mean that doctors can differentiate patients with a poor prognosis from those with a better prognosis and adjust treatment accordingly.
The findings may also change the process of development of new cancer therapies, Glinsky said. Right now, many cancers have very high five-year survival rates, meaning that any trial to prove the superiority of a new treatment is both long and costly.
But with this signature, pharmaceutical companies should be able to try out new therapies on a pre-selected group of patients, cutting down on both time and cost, he said.
"We now need to bring it down to earth and develop tests that would be applicable in every hospital," he said.
One company has already licensed the technology required to detect this signature, and Glinsky said he is pushing for clinical trials to start this summer.
"If everything holds water, we might have a test within a year," he said. "That's my hope."
For more on cancer stem cells, head to the International Society for Stem Cell Research.