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Investigating Genomic Mechanisms of Treatment Resistance in Castration-Resistant Prostate Cancer

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Technical Report,01 May 2012,30 Apr 2017

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University of California, San Francisco San Francisco United States

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Purpose and Scope The purpose of this work is to better understand the mechanisms of resistance to androgen biosynthesis inhibitors in men with castration resistant prostate cancer, and to investigate clinical methods of overcoming resistance. Key Accomplishments and Findings to date 1 Primary endpoint of Phase II study of Dose-Increased Abiraterone Acetate in Men with mCRPC PI Friedlander met, showing that increase in dose of abiraterone at the time of clinical resistance does not result in second PSA declines. 2 A clinical research paper summarizing these findings as well as the CTC work described below was developed and published in Clinical Genitourinary Cancer. 3 CTCs were collected in 41 men with abiraterone-nave mCRPC at baseline on the aforementioned study. Cells have been enumerated for CTCs, CTC clusters, CTCs expressing stem-like and epithelial markers. A trend towards higher CTC counts and lower CTC clusters was observed in patients who were primarily refractory to abiraterone acetate. CD44 expression on CTCs was not correlated with response to abiraterone.4 Array comparative genomic hybridization aCGH of CTC data has been performed in CTCs however the genomic data was of an inconsistent nature due to multiple reasons discussed in the body of this report. 5 Phase I study of Abiraterone Acetate plus ARN-509 in men with mCRPC UCSF PI Friedlander fully accrued, initial results showing PSA declines in men with treated with prior abiraterone and prior chemotherapy observed, indicating activity of this combination. Results presented at 2015 ASCO Annual Meeting and 2015 AACR annual meeting. Manuscript in preparation, and an industry-sponsored Phase III study based on these findings in underway.

Subject Categories:

  • Medicine and Medical Research
  • Genetic Engineering and Molecular Biology
  • Pharmacology

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