Section of Medicine
Chairman: Professor Stan Kaye
Scientific Overview
Introduction
The Section of Medicine is positioned at the interface between The Royal Marsden and The Institute. Its primary remit is to conduct a programme of translational research, which consolidates the link between the two, and a particular focus is on drug development. There are two broad elements:
- A laboratory-based programme, which addresses issues of resistance to conventional treatment in ovarian cancer and prostate cancer. It incorporates studies on the combined use of novel molecularly targeted drugs and conventional agents, and on predictive biomarkers
- A clinically-based programme in our new Drug Development Unit with a Phase I trial portfolio, operated jointly with the Cancer Research UK Centre for Cancer Therapeutics, across a broad range of tumour types. In addition the senior clinicians in the Section are involved in Phase II and III trials in the Gynaecology, Prostate and Sarcoma Units in RMH
Relevance to the NHS Research and Development Programme
Our emphasis is on improvements in the systemic therapy of cancer. A range of avenues are being explored, and our assumption is that the use of conventional chemotherapy and endocrine therapy will continue to increase during the next few years. The challenge is to improve efficacy by dealing with the problem of drug resistance, and obtain best value for the costs involved. In parallel, the demands for novel therapies are ever increasing, and our responsibility is to assess the most promising leads and to identify those patients and tumour types where the benefit is likely to be greatest.
Highlights of 2007
- Continued increase in activity, with 25-30 open Phase I trials, 439 patients referred and 223 patients entered into Phase I trials
- Successful completion of 10 Phase I clinical trials of novel molecular targeted agents, in conjunction with the Pharmacodynamic and Pharmacokinetic Teams in the Centre for Cancer Therapeutics
- Comprehensive definition of high level clinical activity in the CYP17 inhibitor abiraterone in hormone resistant prostate cancer
- First definitive study of single agent clinical activity of a new oral PARP inhibitor in patients with BRCA1/2 associated ovarian cancer
- Established biomarker assay on circulating tumour cells in prostate cancer patients utilising FISH and immunofluorescence for patient selection and PD studies
- Establishment of Professor Robert Brown in new joint Chair in Translational Oncology (with Imperial College London)
- Identification of autotoxin as novel therapeutic target in ovarian cancer
- Identification of PPMID as novel therapeutic target in clear cell ovarian cancer
- Demonstration in preclinical model of in vivo antitumour activity of BGC945 (a-folate receptor targeted TS inhibitor)
Future Aims
- To maintain The Royal Marsden Trust Drug Development Unit’s position as one of the World’s top three such units
- To continue our preclinical studies in ovarian cancer models (in conjunction with Professor Workman’s group) on combination treatment, involving PI3K/AKT pathway inhibitors originating in the CRUK Centre for Cancer Therapeutics, and chemotherapy
- To establish a molecular pathology group, to support our early drug development programme, led by Dr George Thomas
- To establish a programme of work (Ovarian Cancer Action-funded) in aspects of methylation in ovarian cancer, including its role in the control of cancer stem or progenitor cells (Professor Robert Brown)
- To establish molecular characterisation of prostate cancer and ovarian cancer (using ascites) in individual referred patients to support appropriate drug selection
- To evaluate inhibitors of the PI3K/AKT pathway in PTEN -/- castration resistant prostate cancer patients
- To contribute to the detailed clinical evaluation of non-geldanamycin-based HSP90 inhibitors
- To initiate the first Phase I trials of BGC945
- To consolidate our work in conjunction with Professor Alan Ashworth (Breakthrough Breast Cancer Centre) on molecular profiling of ovarian cancer, focusing on the assessment of “BRCAness” in sporadic cases
