Br J Cancer: Olaparib combined with hemi-thoracic radiotherapy to improve the therapeutic index of lung cancer

Radiotherapy is an important local therapy for many cancers, including lung cancer.
However, due to dose-limiting toxicity, the anti-tumor efficacy is still poor.
Therefore, there is an urgent need to formulate related drugs that can increase the anti-tumor effect without increasing the toxicity of normal tissues to improve the effect of radiotherapy.

Reactive oxygen generated by radiation can damage DNA, mainly causing single-strand breaks (SSB).
If not repaired, it will eventually lead to fatal double-strand breaks.
Previous studies have shown that PARP-1 can detect the effects of radiation-induced DNA SSB and recruit DNA repair proteins to repair damaged DNA.

At present, the PARP inhibitor olaparib (olaparib) has been shown to enhance the effect of radiotherapy in a variety of preclinical tumor models including lung cancer, breast cancer , prostate cancer and colon cancer .

However, the effect of its combined effect with radiotherapy on normal tissues has not yet been well studied.
The purpose of this study is to explore the therapeutic index of olaparib combined with hemi-thoracic radiotherapy in a mouse lung cancer model induced by urethane.

Olapanib combined with whole chest radiotherapy can cause normal tissue toxicity

The researchers used olaparib combined with whole-thoracic radiotherapy on A/J mice and monitored body weight changes to assess tolerance and histological evaluation of the effect on normal tissues.
In the anti-tumor (intervention) study, lung tumors were induced by injection of urethane, and then received olaparib, single left chest radiotherapy and olaparib at week 8 (early intervention) and 18 (late intervention), respectively Combined with left chest radiotherapy for treatment.
The anti-tumor efficacy of the above treatments and the effect on normal tissues were evaluated by visual inspection, MRI and histology.

Early intervention of olaparib combined with hemi-thoracic radiotherapy can inhibit the development of lung cancer

The results showed that when olaparib was combined with full-thoracic radiotherapy instead of semi-thoracic radiotherapy, the researchers observed weight loss and increased esophageal toxicity.
In early and late intervention studies, olaparib can improve the anti-tumor effect of hemithoracic radiotherapy without increasing pulmonary toxicity.

All in all, the results of the study revealed that olaparib can increase the therapeutic index of hemi-thoracic radiotherapy in a mouse model of lung cancer .