Recent advances in the design of gene-therapy vectors offer promise for cancer patients who must receive chemotherapy, according to an article published in Nature Reviews Cancer.

In the June 2002 issue, Brian Sorrentino, M.D., director of Experimental Hematology at St. Jude Children's Research Hospital, reviewed the latest developments in gene therapy and offered a roadmap for future research directions.

Scientists and physicians are using gene-therapy approaches to address specific problems involving chemotherapy administration, he wrote. One challenge is that many tumors are resistant to the chemotherapy drugs used to treat cancer. The drugs can also have a toxic effect on the bone marrow. This toxicity can increase the risk of infection or bleeding and can cause patients to need blood or platelet transfusions.

Researchers have also been using gene transfer methods to introduce therapeutic genes into the hematopoietic (blood) stem cells of laboratory animals. These genes are intended to eliminate tumor drug resistance while protecting the normal bone marrow from toxic side effects. Because stem cells can renew themselves and develop into a variety of cell types, they are capable of passing on that protection to other cells in the body. The new cells will also be resistant to the drugs' side effects.

Scientists are now engineering different kinds of vectors-viruses that have been modified so that they can introduce therapeutic genes into specific cells. Numerous studies have shown that these vectors successfully introduce drug-resistant genes into the cells of laboratory animals. But researchers are still attempting to determine if these strategies can be used successfully in humans.

"We predict that in the next few years, we will be able to use novel chemotherapy regimens that overcome tumor cell resistance mechanisms while protecting patients against bone marrow toxicity through the use of modern gene therapy strategies," Sorrentino said. "This should allow us to expand therapeutic opportunities in cancer treatment by widening the gap between tumor cell killing and toxicity to the patient."

Scientists are trying to perfect more efficient gene-transfer techniques so they can genetically modify more stem cells and obtain better responses to chemotherapy. Researchers are also working to create new vector systems and alternate ways of moving genes into stem cells. With additional research, these approaches may soon be widely available to people undergoing chemotherapy, he said.

SOURCES:
Nature Reviews Cancer, June 2002
St. Jude Children's Research Hospital (http://www.stjude.org)