Abstract
Dependent on the stage of the cancer, 25-40% of patients require curative or palliative radiotherapy as part of their primary care treatment. The DNA Damage response (DDR) pathways have been a major area of interest for drug development as tumors often harbor mutations in the DDR pathways. The development of new DDR inhibitors offers wide-ranging opportunities to combine DDR inhibition with radiation therapy. Emerging evidence also supports the use of DDR inhibitors to promote immune stimulatory effects of radiation therapy by further activating the DNA sensing cGAS-STING pathway. DDR inhibitors in combination with RT have been shown to alter PDL-1 expression and have also been linked to modulating cytokine expression to alter the tumor microenvironment. This should be considered in the context of over 300 clinical trials ongoing which are combining immunotherapy with radiotherapy and important clinical studies of this combination therapy which have been published in patients with lung cancer. Significant progress is being made in understanding new drug-radiotherapy combinations and advancing them towards the clinic.
Citation Format: Ricky A. Sharma. Translation to clinical trials: Are we shooting the right arrows at the target? [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-011.