ETD and ECD Mass Spectrometry Fragmentation for the Characterization of Protein Post Translational Modifications

Abstract

Background: Statins have been associated with favorable effects in various solid malignancies. In prostate cancer, statins may synergize with novel anti-androgen agents enzalutamide and abiraterone via pharmacokinetic interactions and by decreasing substrate availability for androgen de-novo biosynthesis. Methods: Medical records of patients with metastatic castration-resistant prostate cancer (mCRPC) between September, 2011 and August, 2016 were reviewed at multiple participating centers. Results: 187 men received abiraterone, while 129 received enzalutamide. Patients treated with enzalutamide had a more advanced disease, with a median overall survival (OS) of 7.8 vs. 18 months in the abiraterone cohort. In the abiraterone cohort, statin use was a statistically significant prognostic factor for longer OS (HR = 0.40, 95% CI = 0.27 to 0.59, p < 0.001) and statin users vs. non users had greater 30% PSA declines rates at 12 wks(77.9 vs. 52.9%, p < .01) In the enzalutamide cohort, statin use was not prognostic for survival or PSA declines. Conclusions: Our study suggests a prognostic effect of statins plus abiraterone but not enzalutamide for mCRPC. The mechanism of this interaction warrants elucidation but may include enhancing the anti-tumor activity of abiraterone as well as cardioprotective effects..