Stem Cells May be Engineered to Resist Toxic Effects of Chemotherapy
A research team led by the National Cancer Institute has taken the first steps toward making bone marrow stem cells resistant to the toxic effects of chemotherapy. Such an advance could potentially allow patients to undergo multiple rounds of high dose chemotherapy without having to remove their marrow, the source of "stem" cells that produce blood and immune system cells.
The researchers focused their work on a gene found not in stem cells but in normal tissue. This gene, called MDR1 (Multi-Drug Resistant), is switched on, and used most often by kidney, colon, and liver cells to help those organs excrete toxic compounds. Cancer cells, however, have learned how to turn on the gene to protect themselves against chemotherapy. Lead researcher Dr. Kenneth Cowan theorized that if stem cells could be engineered to express MDR1 genes, just as some cancer cells do, they could also be protected against chemotherapy.
In this proof-of-principle trial, stem cells were removed from 10 breast cancer patients. The MDR1 gene was inserted in one-half of each patient's stem cells, and the other half received a "dummy" control gene. In six patients for which data are available, Cowan reports that the MDR1 gene had become incorporated in the white blood cells of those patients, while the control gene was detected in only three patients. There was further evidence that MDR1-altered stem cells began populating the bone marrow. This is important because cells that do not adopt the gene will die off when exposed to chemotherapy, allowing the MDR1-active stem cells to progressively expand.
At this point the focus of the technology remains on inserting the genes into the the stem cells, allowing for engraftment into the bone marrow, and allowing for these cells to be present longer than other cells. Once this is proven, MDR1 genetically-engineered stem cells may be helpful in limiting the marrow-related toxicity of chemotherapy. Ultimately, Dr. Cowan hopes that these genes can be inserted along with immunomodulator genes for cancer treatment and for treatment of other diseases such as chronic granulomatous diseases, with the hope of allowing the drug to circulate for a longer amount of time while at the same time minimizing the toxicity.