Timing may not be everything, but it could be important in understanding why an anticancer treatment like radiation produces different results against cancer cells, according to a new study published in the journal Science.
The cells respond differently, the researchers conclude, depending on their state at the time of treatment. Their study tested radiation treatment against human breast cancer cells in which the activity of the cancer-causing gene MDMX was inhibited. The gene, which is often over-expressed in cancers such as melanoma, osteosarcoma, and breast and colorectal cancer, blocks the activity of tumor-suppressing proteins such as p53.
Researchers noted that cancer cells treated with a small interfering RNA to deplete them of MDMX experienced an initial large increase in p53 levels a day after the treatment, and then smaller, oscillating increases afterward.
Radiation treatment aimed at these cells had different impacts, depending on when it was delivered in these cycles. When radiation was delivered during the early peak in p53 production, cell killing was enhanced and it killed off 95 percent of the cells.
By contrast, if radiation was applied during the following phase of oscillatory p53 production, cells were actually protected from the DNA damaging effects of the radiation and the combined treatments killed fewer than 20 percent of the cells.
Thus a quantitative understanding of signal dynamics and cellular states is important for designing an optimal schedule of dual-drug administration.
http://science.sciencemag.org/content/351/6278/1204
Thus a quantitative understanding of signal dynamics and cellular states is important for designing an optimal schedule of dual-drug administration.
http://science.sciencemag.org/content/351/6278/1204
Edited
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