Mechanism of Prostate Cancer Initiation, Progression and Drug Resistance

Primary prostate cancer (PCa) is dependent on androgen receptor signaling for survival and proliferation. Targeting the androgen receptor signaling axis has been standard clinical care. Next generation anti-androgen therapies (ADT) have had clinical success; however, the majority of prostate cancer cases will relapse with castration resistant prostate cancer (CRPC). Over the last decade, next generation sequencing efforts have painted a detailed picture of the highly heterogeneous genomic landscape of the different disease stages of prostate cancer (Localized PCa, Metastatic PCa, and CRPC). On a cellular level, three main mechanisms of ADT resistance are recognized. 1) Reactivation of AR-signaling, 2) Reactivation of the AR oncogenic cistrome by a related nuclear hormone receptor and 3) Lineage plasticity, dedifferentiation to a cellular phenotype that is independent of the drug-target (AR). However, how the plethora of mutations contribute to CRPC is poorly understood. Nor is it known how PCa tumor heterogeneity and microenvironment contributes to the onset of CRPC. Going forward it will be pivotal to gain insight in these complex processes to discover clinical solutions for CRPC.

Mechanisms of PCa progression and drug resistance are poorly understood, in spite of current advances in understanding of the genomic landscape of the different stages of disease. The goal of this Research Topic is to generate a collection of articles with the latest insights into PCa progression and mechanisms of drug resistance. Secondly, generating an overview of current model systems, i.e. organoids, xenograft, PCa cell lines, to study CRPC is a separate objective. Novel model systems to study AR-negative CRPC that underwent lineage plasticity are of great interest to the collection.

For this Research Topic, Original Research articles and Methods papers are preferred. Additionally, Reviews will be considered. Manuscript within the following subjects would be a great addition to this collection.
-Mechanisms of PCa initiation, progression and metastasis
-Mechanisms of drug resistance
-Model systems for prostate cancer research
-Drug targets of CRPC
-CRPC biology and genomics
-Biomarkers for CRPC (subtypes)
-Normal prostate biology relevant to CRPC

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.