Disrupting Gene Repair Mechanism in Cancer Cells May Have Clinical Benefits

Case Western Reserve University researchers have identified a two-pronged therapeutic approach that shows great potential for weakening and then defeating cancer cells. The team's complex mix of genetic and biochemical experiments unearthed a way to increase the presence of a tumor-suppressing protein which, in turn, gives it the strength to direct cancer cells toward a path that leads to their destruction. If the laboratory findings are supported by tests in animal models, the breakthrough could hold the promise of increasing the effectiveness of radiation and chemotherapy in shrinking or even eliminating tumors. The key is to build up a "good" protein - p53-binding protein 1 (53BP1)(see image) -- so that it weakens the cancer cells, leaving them more susceptible to existing cancer-fighting measures. The breakthrough was reported online on November 24, 2014 in PNAS. "Our discovery one day could lead to a gene therapy where extra amounts of 53BP1 will be generated to make cancer cells more vulnerable to cancer treatment," said senior author Youwei Zhang, Ph.D., Assistant Professor of Pharmacology, Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center. "Alternatively, we could design molecules to increase levels of 53BP1 in cancers with the same cancer-killing end result." The cornerstone of the research involves DNA repair - more specifically, double-stand DNA repair. DNA damage is the consequence of an irregular change in the chemical structure of DNA, which in turn damages and even kills cells. The most lethal irregularity to DNA is the DNA double-strand break in the chromosome. DNA double-strand breaks are caused by everything from reactive oxygen components occurring with everyday bodily metabolism to more damaging assaults such as radiation or chemical agents.
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