Repurposing itraconazole as a treatment for advanced prostate cancer: a noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer.
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Androgen receptor gene rearrangements: new perspectives on prostate cancer progression.
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The androgen receptor (AR) is a master regulator transcription factor in normal and cancerous prostate cells. Canonical AR activation requires binding of androgen ligand to the AR ligand binding domain, translocation to the nucleus, and transcriptional activation of AR target genes. This regulatory axis is targeted for systemic therapy of advanced prostate cancer. However, a new paradigm for AR activation in castration-resistant prostate cancer (CRPC) has emerged wherein alternative splicing of AR mRNA promotes synthesis of constitutively active AR variants that lack the AR ligand binding domain (LBD). Recent work has indicated that structural alteration of the AR gene locus represents a key mechanism by which alterations in AR mRNA splicing arise. In this review, we examine the role of truncated AR variants (ARVs) and their corresponding genomic origins in models of prostate cancer progression, as well as the challenges they pose to the current standard of prostate cancer therapies targeting the AR ligand binding domain. Since ARVs lack the COOH-terminal LBD, the genesis of these AR gene rearrangements and their resulting ARVs provides strong rationale for the pursuit of new avenues of therapeutic intervention targeted at the AR NH2-terminal domain. We further suggest that genomic events leading to ARV expression could act as novel biomarkers of disease progression that may guide the optimal use of current and next-generation AR-targeted therapy. (+info)
Population-based study on use of chemotherapy in men with castration resistant prostate cancer.
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PXD101 potentiates hormonal therapy and prevents the onset of castration-resistant phenotype modulating androgen receptor, HSP90, and CRM1 in preclinical models of prostate cancer.
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The role of intracrine androgen metabolism, androgen receptor and apoptosis in the survival and recurrence of prostate cancer during androgen deprivation therapy.
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Prostate cancer (CaP) is the most frequently diagnosed cancer and leading cause of cancer death in American men. Almost all men present with advanced CaP and some men who fail potentially curative therapy are treated with androgen deprivation therapy (ADT). ADT is not curative and CaP recurs as the lethal phenotype. The goal of this review is to apply our current understanding of CaP and castration-recurrent CaP (CR-CaP) to earlier studies that characterized ADT and the molecular mechanisms that facilitate the transition from androgen-stimulated CaP to CR-CaP. Reexamination of earlier studies also may provide a better understanding of how more newly recognized mechanisms, such as intracrine metabolism, may be involved with the early events that allow CaP survival after initiation of ADT and subsequent development of CR-CaP. (+info)
Docetaxel chemotherapy for Chinese patients with castrate-resistant prostate cancer.
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