A research team at Duke University, led by Dartmouth and Duke professors, discovered a treatment method that has brought researchers one step closer to a cure for drug-resistant leukemia. Pharmacology and toxicology professor Manabu Kurokawa and Sally Kornbluth, a pharmacology and cancer biology professor of at Duke University School of Medicine, led the team to discover a way to destroy a patient's cancer cells using mutations within certain cells.
Kurokawa's research focuses on chronic myeloid leukemia, a type of white blood cell cancer that can easily become resistant to drug treatments, he said. Gleevec is the most common drug used to treat this leukemia, but it can eventually become ineffective if cells become resistant. Chronic myeloid leukemia is caused by a specific oncoprotein called BCR-ABL, a mutated protein that makes a cell cancerous, according to Kurokawa.
BCR-ABL is only present in patients with this type of cancer.
The most common way to treat chronic myeloid leukemia is to use drugs that will inhibit the mutated protein. Kurokawa and Kornbluth focused, however, on using the protein to kill leukemia by targeting only cells that exhibit BCR-ABL, according to Kurokawa. This will prevent healthy, non-cancerous cells from being killed, since they do not have the BCR-ABL oncoprotein.
While traditional chemotherapy can affect healthy cells, the researchers' new method only targets cancerous cells.
"Our idea was to approach BCR and not inhibit it," Kurokawa said. "As long as activity exists, our gene therapy becomes activated."
The gene therapy works even when the cancer cells become resistant to drugs, because it specifically targets the protein that actually causes the cancer, which is less likely to mutate, he said.
This new strategy could change the way oncologists use technology to treat cancer, pharmacology and toxicology professor Alan Eastman said.
"From a technological point of view, this is a really exciting approach," Eastman said. "The strategy that only tumor cells will die because only tumor cells have the mutant protein is an exciting direction for the future."
The team's research is significant to the field because it only targets the harmful cells, pharmacology and toxicology professor Yolanda Sanchez said.
"This is a new way of thinking about cancer therapy taking advantage of the changes that the leukemia cells are dependent on," Sanchez said.
This method is still being tested, and will not be used on a large scale in the near future, Kurokawa said.
This new form of treatment could be used to help chronic myeloid leukemia patients in smaller ways, such as "cleaning" bone marrow, he said, referring to a process in which cancer patients use their own bone marrow in transplants. The treatment is used when a bone marrow transplant canot be found for a patient, and it requires that bone marrow be removed, put through chemotherapy to kill the leukemia cells and then put back in the patient's body.
This form of bone marrow transplant, however, still presents problems, Kurokawa said.
"There is a chance that there will still be leukemia in the cells, and then the leukemia reenters the body," he said.
Only cells with BCR-ABL would be targeted using the new approach, which would remove all of the cancer cells in the bone marrow and not affect any of the healthy cells, effectively cleaning the marrow.
Eastman said that there are other problems with cleaning bone marrow. There is the potential that not all the cells with the mutant protein will be destroyed by the gene therapy and some cancer cells could survive.
"If you can't get into all the cells, there is still a population that can succumb to leukemia," he said.
However, Eastman acknowledged that this form of gene therapy could still be "extremely valuable" to certain leukemia patients.
The team began their research started at Duke six years ago, according to Kurokawa. While his lab at the Geisel School of Medicine is still small, he said he hopes to continue working to solve drug-resistant chronic myeloid leukemia.
Kornbluth could not be reached for comment by press time.
