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Patients’ own stem cells may protect against toxins of chemotherapy

Chemotherapy saves lives, but it also kills healthy tissue like bone marrow. According to a new study involving three patients with glioblastoma, a deadly cancer of the brain, stem cells from cancer patients’ own blood may protect their bone marrow from the toxic effects of treatment.

Glioblastomas often carry an active form of a gene called MGMT, which is a DNA repair enzyme that protects the cancer cells against chemotherapy. To overcome that protective effect, doctors use benzylguanine, a drug that blocks MGMT – but that drug also makes bone marrow and blood cells vulnerable. For this study, scientists at Fred Hutchinson Cancer Research Center in Washington took a different approach by transplanting gene-modified stem cells into study participants.

From a release:

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. “P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine,” [lead author Hans-Peter Kiem, MD] said.

“This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded,” said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiem’s lab.

The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.

paper on the work appears today in Science Translational Medicine.  The clinical trial is ongoing and more research is needed to see whether the potential treatment will work for others.

Previously: Clinical trials: my next good chance, In-womb exposure to chemotherapy appears safe for babies and New discovery suggests tumor suppression can be had without killing healthy cells
Photo by the National Cancer Institute

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