Blocking POLQ gene could improve radiotherapy results
This was a very interesting article I came across in Cancer Research while looking for something else. Serendipity is a great thing sometimes. A quote in the abstract caught my eye:
"We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity."
Essentially, the researchers found that if they blocked the POLQ gene, which has a role in repairing damaged DNA, then radiotherapy was more effective. What's more, POLQ knockdown has minimal effect on normal tissue, so blocking the gene did not have any effect on the sensitivity of normal tissue to radiation. This makes the gene an ideal target since it is more specific to, and abundant in, cancer cells.
The article stated that:
"Radiotherapy is a vital tool in the management of cancer patients. It is often given with curative intent either alone or with chemotherapy in patients with diseases as diverse as head and neck, cervix, bladder, and non–small cell lung cancer. The radiation dose that can safely be delivered to patients is limited by the dose tolerances of surrounding normal tissues. It is anticipated that the effectiveness of radiotherapy would be improved if tumor cells could be rendered more sensitive to ionizing radiation (IR) without altering the sensitivity of normal tissues."
It is therefore possible that POLQ inhibition might be used clinically to cause tumour-specific radiosensitisation. In other words, if a new drug could be developed to block POLQ it might allow radiotherapy to be more effective without impacting normal surrounding tissues too much.
Higgins, G., Prevo, R., Lee, Y., Helleday, T., Muschel, R., Taylor, S., Yoshimura, M., Hickson, I., Bernhard, E., & McKenna, W. (2010). A Small Interfering RNA Screen of Genes Involved in DNA Repair Identifies Tumor-Specific Radiosensitization by POLQ Knockdown Cancer Research, 70 (7), 2984-2993 DOI: 10.1158/0008-5472.CAN-09-4040
One Response to “Blocking POLQ gene could improve radiotherapy results”
Inhibiting PARP may also potentiate radiotherapy, but we’ve yet to see any significant trial activity in that direction. It will be interesting to see how this develops!
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