Gene-therapy advances offer hope to chemotherapy patients

St. Jude Children's Research Hospital (ALSAC)
Friday, 31 May 2002

New strategies protect patients from toxic side effects while allowing more aggressive cancer treatments

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, reviews the latest developments in gene therapy and offers a roadmap for future research directions.

Scientists and physicians are using gene-therapy approaches to address specific problems involving chemotherapy administration. 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 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 worldwide and at St. Jude are 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.

St. Jude Children's Research Hospital, in Memphis, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through funds raised by ALSAC. ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children's Research Hospital. Families without insurance are never asked to pay.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org