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Abstract:

Purpose/objective In patients with locally advanced rectal cancer, the addition of the PARP inhibitor olaparib might have the potential to intensify standard chemoradiation. This intensification could lead to better overall survival by reducing local and distal recurrence and to higher pathological complete response rate, enlarging the group of patients in whom a non-surgical approach can be considered. In the current study, we performed a tumor growth delay assay in a rectal cancer mouse model exposed to ionizing radiation (IR) and/or olaparib to explore the enhancing potential of olaparib in vivo. Material/Methods Twenty-four HCT116 xenografted MRI nu/nu mice were randomized in 4 groups: control, IR (10 Gy single dose on the tumor), olaparib (30 mg/kg 26 hours and 2 hours prior to IR and 22 hours after IR) and IR + olaparib. Half of the mice were followed until the tumor volume doubled compared to the volume at the start of treatment. The other half were sacrificed immediately after the end of treatment to assess direct molecular changes. Results Double tumor volume was reached in the control group and the olaparib group respectively after 22 and 19 days. In the IR group, early death of one of the mice on day 28 impeded full tumor growth delay assay. However, relative tumor volume then was nearly doubled (1.89 times the original volume). The combination of IR and olaparib delayed tumor doubling time to 47 days after IR. Conclusion When added to ionizing radiation, olaparib shows an increased tumor volume doubling time compared to IR only in an in vivo rectal cancer model. Olaparib only does not show an improvement. This in vivo experiment shows the potential of adding a PARP inhibitor to the treatment schedule for rectal cancer patients.