Assessing the Androgen indifferent prostate cancer patients reponse to novel antiandrogen-based regimen or taxanes.

Androgens are hormones that are important for normal male sexual development. Androgen receptors allow the body to respond appropriately to these hormones. Testosterone is an androgen that promotes prostate cancer cell proliferation through the activation of androgen receptor. Both players are needed for cell proliferation in prostate cancer cells. For these reasons, testosterone and its receptor, namely, the Androgen Receptor (AR) have been targetted for impairing prostate cancer growth and progression. However, the recent development of novel anti-androgen therapies (ARTAs) has challenged the perception that prostate cancer proliferation and progression always depend on these two players alone. The diverse responses to these recently approved therapies with distinct mechanisms of action have exposed the biological heterogeneity/diversity of prostate cancer cells and illustrated the urgent need to apply our understanding of prostate cancer biology to clinical decision-making. To overcome this unmet need, some authors introduced the concept of Androgen indifferent prostate cancer (AIPC) variants to define those prostate cancer phenotypes (the set of observable characteristics or traits of an organism) that do not depend on testosterone and AR to proliferate and progress. The AIPC entity is an umbrella term that includes several clinical entities. Among these entities, the investigator will focus on the one called Aggressive Variant Prostate Cancer (AVPC). Since the ARTAs introduction and extensive use in prostate cancer, the androgen indifferent phenotype is becoming an increasingly common clinically meaningful entity. Among these clinical entities, the investigators will explore whether the clinical criteria for AVPC, truly identify patients not responding to novel anti-androgen therapies (ARTAs), their combinations, or androgen deprivation therapy alone. We will study AVPC as this is the most aggressive form of advanced prostate cancer, as its name suggests. The identification of the AVPC phenotype based on clinical criteria may potentially spare patients from potential side effects related to these therapies targeting androgen receptor, such as major cardiac events (MACES). The results of our work may affect clinical trial inclusion criteria, sparing AIPC/AVPC patients from receiving AR targeting agents. In case these clinical criteria fail to identify the refractory phenotypes, the analysis on the most informative intermediate clinical endpoint may expedite future clinical trial by shortening the required follow-up of future studies.