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Brain tumor radiation resistance defeated

Science News, December 10, 2009

One of the biggest challenges to the treatment of cancer is overcoming the ability of cancer cells to become resistant to drugs or radiation. The problem of resistance is particularly relevant in brain cancers called gliomas. Research published in the Journal Stem Cells reports one method of overcoming this problem.

Scientists at Duke University and the Cleveland Clinic claim to have identified molecules associated with the ability of certain cells within a glioma, called tumor stem cells, to resist radiation. Specifically, they have identified a protein called "Notch", which is normally involved in embryonic development, that seems to be selectively found in resistant cells. Using genetic engineering methods they have made cells that were previously sensitive to radiation to become resistant by inducing expression of Notch.

Dr. Jialiang Wang of Duke University, who is the lead author of the study. said the finding marked the first report that Notch signaling in tumor tissue is related to the failure of radiation treatments.

"This makes the Notch pathway an attractive drug target," Wang said. "The right drug may be able to stop the real bad guys, the glioma stem cells." The authors have also demonstrated that by inhibiting activity of the Notch protein, through administration of chemicals known as gamma-secretase inhibitors, can result in making resistant cells sensitive to radiation.

These findings are interesting in light of another very recent publication (Zhen et al. Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas. Cancer Lett. 2009 Dec 3) in which the anti-leukemic drug Arsenic Trioxide was also demonstrated to alter glioma stem cells through manipulation of the Notch pathway. Notch has been found in numerous other types of tumor stem cells such as breast, colon, lung, and prostate cancer. The expression of a protein in cancer cells that is supposed to be only expressed during embryonic development supports the theory that during formation of cancer, mature cells tend to revert to an embryonic-like phenotype. This is also exemplified by the fact that adding cancer genes (oncogenes) in combination with some specific proteins can take an adult skin cell and transform it into a cell that resembles the embryonic stem cell, called an "iPS" cell. This is described in the following video:

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