Molecular Mechanisms of Disease Progression and the Development of Novel Treatment Strategies in Advanced Prostate Cancer (Northern Prostate Cancer Collaborative (ProMPT))

OBJECTIVES:

• To study molecular pathology and mechanisms of disease progression.
• To develop novel treatment strategies for patients with advanced prostate cancer.
• To evaluate novel markers and treatment and epidemiological approaches.

OUTLINE: This is a multicenter study.

• Program I (Molecular Signaling in Advanced Prostate Cancer): Researchers from Newcastle, York, and Bristol analyze androgen receptor (AR) (i.e., AR regulated genes and AR co-activators and co-repressors) and fibroblast growth factor (FGF) signaling and examine the cross-talk between these two systems and the insulin-like growth factor (IGF) axis.
• Program II (Mechanisms of Skeletal Metastases): Researchers from Newcastle, Sheffield, Bristol, and Manchester analyze mechanisms of skeletal metastases and candidate factors responsible for skeletal metastases (e.g., BMP-6, TGF-β1, IL-6, and IL-6 receptor). The balance between proteases and their inhibitors is also analyzed.
• Program III (Prostate Targeting, Models, and Novel Approaches to Therapy): Researchers from Newcastle, Sheffield, York, and Manchester analyze and develop reagents and methods that will facilitate novel gene-based approaches to therapy, including prostate tissue specific gene expression, model systems of gene function and therapeutic studies, translational gene-based therapies, and effectors for potential gene therapy.
• Program IV (Developmental Therapeutics): Researchers from Newcastle, York, and Manchester analyze novel proteins identified during the study to synthesize novel reagents aimed at disrupting pathways and signaling molecules that have been shown to be of critical importance to prostate cancer (e.g., AR and FGF signaling).
• Program V (Biorepository and Database): Tissue, DNA, blood, serum, and urine samples from Newcastle, Sheffield, and Manchester biorepositories are stored and used for analysis in programs I-IV. Support for tissue and data collection as well as database management is provided to enable these resources to be made available to the wider research community.
• Program VI (Clinical Trials and Health Services Research): Researchers from Newcastle, Sheffield, Manchester, and Bristol participate in phase I trials using dendritic cells and gene-directed enzyme prodrug therapy (GDEPT) approaches to analyze environmental interactions with the genotype and evaluate prevention strategies (e.g., diet) that may underlie variations in the incidence of prostate cancer.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.