ESTRO 2020 Abstract book

S1070 ESTRO 2020

PO‐1825 Abiraterone sensitises response to high dose radiotherapy in prostate & bone cancer models in vitro. T. Wright 1 , K. Prise 1 , A. Cole 1 1 Queen's University Belfast, Center for Cancer Research and Cell Biology, Belfast, United Kingdom Purpose or Objective Both Abiraterone acetate and Enzalutamide are novel anti- androgens shown to improve progression-free survival and overall survival in patients with metastatic castration- resistant prostate cancer. However, there still exists questions with regards to their efficacy and toxicity when combined with radiation strategies, with recent studies suggesting an increased risk of fracture when Abiraterone is combined with radium-223 treatment. In this study, we aimed to evaluate the impact of Abiraterone acetate and Enzalutamide using bone (SJSA-1, SAOS-2) androgen-sensitive (LNCaP) and castration- resistant (PC3) human prostate cancer cell lines both as single agents and investigate potential radiosensitisation effects when combined with standard X-ray radiotherapy and in combination with Radium-223. Material and Methods Cell viability studies were conducted using MTT assay. Human prostate cancer cell lines LNCaP (androgen- sensitive), PC3 (androgen insensitive) and both SAOS-2 and SJSA-1 (bone osteosarcoma) were treated with a dose range of 10nM-100μM Abiraterone or Enzalutamide. Following 72 hours, viability was determined through comparison to untreated controls and significance evaluated through use of standard deviation. Colony formation assays were used to assess combination of treatment of agents and ionising radiation. Cell were pre-treated with 10μM Abiraterone or Enzalutamide (previously determined in prior viability study) one-hour pre irradiation and irradiated at a dose range of 0-8Gy. Survival fraction was calculated through control comparison and standard deviation used to determine significance. For Radium-223 studies, models were exposed to Radium- 223 for either 6 or 24 hour periods at calculated dose ranges of 0-0.5Gy. Plates were then washed multiple times with PBS to remove all traces of Radium and colony formation assay carried out as described. Results In combination with x-ray across all models, pre-treatment with Abiraterone prior to irradiation resulted in a significant reduction in survival fraction compared to irradiation alone at doses of 4Gy and above (Figure 1). Suggesting that abiraterone can radiosensitise not only androgen-dependent and androgen-independent human prostate cancer models, but osteoblastic bone models as well. This result, therefore, suggests the existence of an independent mechanism of action for Abiraterone, which is not dependent on the attenuation of androgen receptor signalling. Replication of these experiments with the alpha source radium-223 showed no significant sensitisation effects when combined with either Abiraterone or Enzalutamide (Figure 2). With this loss of sensitisation potentially resultant from the highly ionising impact of Radium-223.

Conclusion This work indicates the potential for SPIONs to be used as radiosensitisers for the combination of radiotherapy with MRI. It has potential to be used both diagnostically and therapeutically. However, clonogenic assays with 225kVp x-rays indicated a cell line specific radiosensitisation with SPIONs, suggesting their benefit may be limited to certain treatment sites. Ongoing work is investigating the uptake of SPIONs within the cells through ICP-MS, in order to relate SPION intracellular concentration to biological effects.