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Development of novel targeted therapeutics for prostate cancer

Professor de Bono has a primary interest in biomarker driven early anticancer drug development but also focuses on developing novel targeted therapeutics for the treatment of patients with metastatic castration refractory prostate cancer (CRPC) in collaboration with Professor David Dearnaley and Dr Chris Parker.

With a dedicated multidisciplinary team comprising research nurses, data managers, clinical trial co-ordinators, biomedical scientists, a Clinical Lecturer in Dr Gerhardt Attard, and several clinical and translational clinical research fellows dedicated to translational research in advanced prostate cancer we treat more than 100 patients with late stage CRPC on clinical trials every year.

These patients are being recruited to rationally designed trials of molecularly targeted agents that are aiming to make this disease a disease that can be controlled for long periods of time.

Key goals for this research team include:

  • The analytical validation and clinical qualification of intermediate endpoints of overall survival.
  • The molecular stratification of advanced prostate cancer to deliver personalized medicine through the concurrent evaluation of putative predictive biomarkers during clinical drug development.
  • The utilization of circulating tumour cells as multi-purpose biomarkers in advanced prostate cancer.
  • The study of circulating plasma DNA in advanced prostate cancer patients.
  • The dissection of resistance to current treatments including abiraterone acetate.
  • The targeting of continued androgen receptor signalling, through for example novel anti-androgens, a locked antisense therapeutic to the androgen receptor, and androgen receptor degrading drugs including heat shock protein inhibitors.
  • The targeting of the PI3K/AKT/TOR kinase in advanced prostate cancer exhibiting PTEN loss.
  • The targeting of the ETS oncogenes by various therapeutic strategies.
  • The evaluation of BRCAness in sporadic prostate cancer, and the treatment of BRCA2 carrier patients with advanced prostate cancer with PARP inhibitors.

With clinical fellows, this team has led on the successful development of the androgen biosynthesis inhibitor abiraterone acetate (a compound generated by ICR chemists) as well as cabazitaxel. We are now studying a number of putative resistance mechanisms through reiterative research strategies.

We have been successfully collecting tumour biopsies from patients with castration resistant and advanced prostate cancer as well as the matched pre-treatment, hormone sensitive, tumour material for these molecular analyses. We are pursuing similar molecular studies in both circulating tumour cells and circulating plasma nucleic acids.


External funding:

Cancer Research UK; The Department of Health; The Medical Research Council; Prostate Cancer UK; The Prostate Cancer Foundation (CA; USA); the Movember Foundation.


 
 

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Early Anti Cancer Clinical Drug Development Development of novel targeted therapeutics for prostate cancer Utilising Biomarkers