Inhibition of RAD51 Repair Protein Enhances Radiotherapy

Patrick Yang ‘20

RAD51 radiotherapy.jpeg

Figure 1. One of the most aggressive forms of brain cancer can become more receptive to radiotherapy after RAD51 inhibition.

Despite intensive radiotherapy and treatment, glioblastoma, an aggressive form of brain cancer, is often fatal. It is widely believed that a subgroup of glioblastoma cells, called glioblastoma stem cells, is responsible for treatment resistance because the cancer’s DNA damage response is localized in these cells. The discovery and manipulation of the mechanism for the upregulation of DNA damage response in glioblastoma stem cells would increase efficacy of radiotherapy. Researchers led by Dr. Susan Short of the University of Leeds attributed the DNA damage response of glioblastoma stem cells to their high concentration of the repair protein, RAD51. Inhibiting this protein might radiosensitize glioblastoma stem cells, or make them vulnerable to radiation, therefore increasing treatment success.

Dr. Short and her team tested the extent of radiosensitization following inhibition of RAD51 by measuring the radiation dose needed to achieve 50% cell death before and after treatment with RAD51 inhibitors. Three different strains of glioblastoma stem cells were exposed to radiation doses of 1 to 5 Gy (1 joule of radiation per kilogram). The mean radiation dose that achieved 50% cell death was 2.69 Gy. After the cells were treated with RI-1 and B02, two of many RAD51 inhibitors that inhibit DNA recombination and repair, the mean radiation dose to achieve 50% cell death was 1.94 and 1.87 Gy, respectively. This decrease in radiation dosages of untreated and treated strains resulted in a statistically significant difference in survival, which demonstrates that radiosensitization can be accomplished by using RAD51 inhibitors.

More investigation will be required to discover the exact mechanism behind radiosensitization after RAD51 inhibition, but results show that RAD51 is a valid target when considering radiotherapy enhancement. This novel approach towards enhancing radiotherapy – inhibiting DNA repair mechanisms in cancerous cells – is a new and hopeful advance towards treating aggressive cancers.

 

References:

  1. H.O. King, et al., RAD51 is a selective DNA repair target to radiosensitize glioma stem cells. Stem Cell Reports 8, 125-139 (2017). doi: 10.1016/j.stemcr.2016.12.005.
  2. Image retrieved from: https://www.flickr.com/photos/urologysa/8200563956
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