Preclinical models of prostate cancer - modelling androgen dependency and castration resistance in vitro, ex vivo and in vivo

Prostate cancer is well known to be dependent on the androgen receptor (AR) for growth and survival. Thus, AR is the main pharmacological target to treat this disease. However, after an initially positive response to AR-targeting therapies, prostate cancer will eventually evolve to castration-resistant prostate cancer, which is often lethal. Tumour growth was initially thought to become androgen-independent following treatments; however, results from molecular studies have shown that most resistance mechanisms involve the reactivation of AR. Consequently, tumour cells become resistant to castration - the blockade of testicular androgens - and not independent of AR per se. However, confusion still remains on how to properly define preclinical models of prostate cancer, including cell lines. Most cell lines were isolated from patients for cell culture after evolution of the tumour to castration-resistant prostate cancer, but not all of these cell lines are described as castration resistant. Moreover, castration refers to the blockade of testosterone production by the testes; thus, even the concept of castration in vitro is questionable. To ensure maximal transfer of knowledge from scientific research to the clinic, understanding the limitations and advantages of preclinical models, as well as how these models recapitulate cancer cell androgen dependency and can be used to study castration resistance mechanisms, is essential. Prostate cancer depends on the hormonal environment for growth. In this Review, the authors describe how this hormonal dependency can be studied in preclinical models. Advantages and limitations of these models are discussed to maximize the transfer of knowledge from scientific research to clinical applications.

Automated summary

Prostate cancer depends on androgen receptor (AR) for growth and survival, making it the main target for pharmacological treatment. However, prostate cancer eventually becomes castration-resistant, with most resistance mechanisms involving reactivation of AR. The definition of preclinical models and cell lines for studying prostate cancer and castration resistance is still unclear. Understanding the limitations and advantages of these models is crucial for effective translation of scientific knowledge to clinical applications. Evaluation: x/10