Radiotherapy is widely used to treat many different types of cancer. While highly effective at killing cancer cells, radiotherapy can also damage surrounding healthy tissues, causing side effects that may persist long after treatment. These risks often limit the dose of radiotherapy that clinicians can safely deliver.
One approach to improving outcomes is to combine radiotherapy with drugs that selectively increase the sensitivity of tumour cells to radiation. Such radiosensitising treatments have the potential to improve tumour control without increasing damage to normal tissues.
The new study focuses on the potential of DNA polymerase theta (Polθ) in this setting. Polθ is an important enzyme involved in the repair of DNA double strand breaks (DSBs). Previous work from the Higgins lab demonstrated that inhibiting Polθ is a safe and effective approach for tumour selective radiosensitation in preclinical models. However, no clinically actionable biomarkers existed to identify patients most likely to benefit.