A number of agents have begun testing for this project. One agent, a MEK inhibitor, has been evaluated as a radiation sensitizer both in vitro and in vivo. The agent was found to sensitize three histologies to radiation in vitro and to sensitize two tested cell lines to radiation in subcutaneous xenografts. Additional mechanistic work has revealed that the cause of this senstization appears to be related to abrogation of the G2 checkpoint after irradiation. The initial results of these studies have been submitted for publication. Additional work with this compound is focusing on possible biomarkers of effect to identify candidate markers of efficacy for clinical translation. Two additional agents are currently undergoing testing for efficacy as radiation sensitizers. These include a small molecule poly(ADP-ribose) polymerase (PARP) inhibitor and a multi-target tyrosine kinase inhibitor. The preliminary in vitro clonogenic assays have been promising for these two compounds. Additional in vitro work, in vivo work, and mechanistic work will be ongoing. The eventual goal for these compounds is clinical translation into trials as radiation sensitizers.
| Reed, Aaron; Valle, Luca F; Shankavaram, Uma et al. (2017) Effect of Prostate Magnetic Resonance Imaging/Ultrasound Fusion-guided Biopsy on Radiation Treatment Recommendations. Int J Radiat Oncol Biol Phys 97:947-951 |
| Citrin, Deborah E (2016) Short-Term Screening Assays for the Identification of Therapeutics for Cancer. Cancer Res 76:3443-5 |
| Premo, Christopher; Apolo, Andrea B; Agarwal, Piyush K et al. (2015) Trimodality therapy in bladder cancer: who, what, and when? Urol Clin North Am 42:169-80, vii |
| Citrin, Deborah E; Mitchell, James B (2014) Altering the response to radiation: sensitizers and protectors. Semin Oncol 41:848-59 |
