ProMPT - Prostate Cancer: Mechanisms of Progression and Treatment

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Future Priorities


Programme I: Molecular Pathology of Progressing Prostate Cancer (Cambridge & Newcastle)

I.A. Complete information on temporal recruitment of androgen receptor (AR) co-regulators to androgen responsive gene promoters (including PSA promoter/ enhancer regions). Determine the effects of siRNA knock-down of specific AR co-regulators on the expression of AR regulated genes.

I.B. In Cambridge to continue work on the new genomic binding sites identified through the initial one year?s work (EMBO Reports, 2007).

Programme II: Mechanisms of skeletal metastases (Sheffield & Manchester)

II.A. To complete investigation of the effects of Osteoprotegerin (OPG) on tumour growth in bone using established xenograft models and to identify OPG isoforms produced by tumour.

II.B. Interrogation of mechanisms of lipid handling in prostate cancer metastasis using chemometric analysis Determination of influence of human bone marrow lipids on migration, with focus on the Caveolin-1 / CD36 axis.

Programme III: Cell Models (York & Manchester)

III.A. To determine the tumour-initiating population from prostate tumours, either directly from patient?s samples or from xenografted tissue samples. Carry out sequential xenografting of stem cell derived material, employing phenotypically tagged tumours if possible to track tumour development and behaviour from both orthotopic and subcutaneous sites. The latter has the added advantage of screening out non- tumourigenic cells.

To improve and maintain isolator environment for mouse colony and exploit multiphoton microscopy for tumour tracking. Maintaining a breeding colony of transgenic mice (Rag2-/-GC-/-) for the production of neoplasms which is also suitable for metastasis studies. Provide cellular material/facilities for collaborative studies (both mechanistic and translational).

III.B. To isolate ?unexpanded? stem cell isolates from primary prostate cancer and establish high through put genomic studies in collaboration with EPISTEM (Manchester).

Programme IV: Developmental Therapeutics (Newcastle)

IV. Complete development of agents that inhibit TIP60 with the intention by end of year one to optimize selectivity profiles and pharmacological properties of Tip60 inhibitors.

Programme VI: Epidemiology; Genetic Epidemiology; Clinical & Health Services Research.

VI.A Undertake aetiological and genetic epidemiological analyses within the ProtecT case-control series and publish findings.


In Manchester establishment of a window trial of AZD4054 in prostate cancer. Development and analysis of novel biomarkers (apoptosis / angiogenesis / circulating cells + DNA) and advanced molecular imaging in measurement of prostate cancer staging, progression and response to treatment.

In Cambridge, establishment of pre-operative trials of novel agents coupled with biological endpoints.

Programme V: Bio-repository & database (Bristol, Cambridge, Manchester, Newcastle and Sheffield)

V.A To develop web-based software for collection of clinically linked information.

V.B To continue DNA & serum bio-repository collection from ProtecT (~50,000 men per year)

V.C Complete tissue micro-array (TMA) from 500 men treated by surgery, and from hormone na´ve and resistant disease (Cambridge, Manchester, Newcastle & Sheffield).

VI Create a repository of cleaned and derived clinical, epidemiological and genetic data from the ProtecT study, including the case-control series described in Research section above. Build a database of molecular assay data linked to the ProtecT study data.

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