In the last few years, several new drugs with various mechanisms of action have been approved for the treatment of castration-resistant prostate cancer. Due to this development, therapeutic decision-making has become increasingly complex. Therefore, therapy selection as well as timing and sequence of treatments need to be optimized in an individual manner. In addition, also for these novel therapies, baseline and acquired as well as cross-resistance have been observed. Underlying mechanisms become increasingly clear, resulting in a shift from empiric-based towards rational- based therapeutic decision-making. In the present review, we provide an overview on the resistance mechanisms against the most frequently applied systemic treatments of metastatic castration-resistant prostate cancer such as docetaxel, abiraterone and enzalutamide. We summarize - among others - the mechanisms by MDR (multidrugresistant) protein expression, alterations of androgen receptor, Wnt, p53 and DNA-repair pathways (BRCA/ATM) as well as resistance through therapy-induced neuroendocrine differentiation of the tumour.
|Translated title of the contribution||Molecular underpinnings of systemic treatment resistance in metastatic castration-resistant prostate cancer|
|Number of pages||8|
|Publication status||Published - May 2020|
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