Cell Line Characteristics Predict Subsequent Resistance to Androgen Receptor-Targeted Agents (ARTA) in Preclinical Models of Prostate Cancer.

Treatment of prostate cancer (PCa) has changed considerably in the last decade due to the introduction of novel androgen receptor (AR)-targeted agents (ARTAs) for patients progressing on androgen deprivation therapy (ADT). Preclinical research however still relies heavily on AR-negative cell line models. In order to investigate potential differences in castration-resistant PCa (CRPC) growth, we set out to create a comprehensive panel of ARTA-progressive models from 4 androgen-responsive AR wild-type PCa cell lines and analyzed its androgen response as opposed to its ADT-progressive counterparts.

Androgen receptor signalling impairs docetaxel efficacy in castration-resistant prostate cancer.

Androgen receptor (AR) signalling drives neoplastic growth and therapy resistance in prostate cancer. Recent clinical data show that docetaxel combined with androgen deprivation therapy improves outcome in hormone-sensitive disease. We studied whether testosterone and AR signalling interferes with docetaxel treatment efficacy in castration-resistant prostate cancer (CRPC).

A bypass mechanism of abiraterone-resistant prostate cancer: Accumulating CYP17A1 substrates activate androgen receptor signaling.

Background: Intratumoral steroidogenesis and its potential relevance in castration-resistant prostate cancer (CRPC) and in cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1)-inhibitor treated hormone-naïve and patients with CRPC are not well established. In this study, we tested if substrates for de novo steroidogenesis accumulating during CYP17A1 inhibition may drive cell growth in relevant preclinical models.

Methods: PCa cell lines and their respective CRPC sublines were used to model CRPC in vitro.