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Source of cancer stem cells’ resistance to radiation discovered at Stanford

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Much to the dismay of patients and physicians, cancer stem cells — tiny powerhouses that generate and maintain tumor growth in many types of cancers — are relatively resistant to the ionizing radiation often used as therapy for these conditions. Part of the reason, say researchers at Stanford University School of Medicine, is the presence of a protective pathway meant to shield normal stem cells from DNA damage. When the researchers blocked this pathway, the cells became more susceptible to radiation.

“Our ultimate goal is to come up with a therapy that knocks out the cancer stem cells,” said Robert Cho, MD, a clinical instructor of pediatrics. “If you irradiate a tumor and kill a lot of it but leave the cancer stem cells behind, the tumor has the ability to grow back.” As a result, patients can relapse months or years after seemingly successful treatment.

Cho and radiation oncologist and post-doctoral fellow Maximilian Diehn, MD, PhD, are co-first authors of the research, which was published on Feb. 4 in Nature. They collaborated with scientists at Stanford and City of Hope National Medical Center to conduct the research. They studied breast epithelial stem cells from humans and mice to unravel why cancer stem cells are more resistant to radiation than other cancer cells.

“Since cancer stem cells appear to be responsible for driving and maintaining tumor growth in many tumors, it is critical to understand the mechanisms by which these cells resist commonly used therapies such as chemotherapy and radiotherapy,” said Diehn. “Ultimately, we hope to improve patient outcomes by developing therapeutic approaches that directly target cancer stem cells or that overcome their resistance mechanisms.”

The origin of cancer stem cells is still under debate. Some may arise from normal adult stem cells gone awry. Others may represent specialized cells from adult tissues that have acquired a stem-cell-like state through a series of mutations. What’s clear is that cancer stem cells can reconstitute an entire tumor cell population when transplanted into an immune-deficient animal, and destroying them is likely to be critical in order to stop the growth and spread of the disease.

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