Principal investigator: Per-Uno Malmström
Urological cancer is increasing in number. The available diagnostic and therapeutic methods have several disadvantages. We aim to develop more specific instruments for the clinician and more effective treatments for the patients. The Unit of Experimental Urology at the Rudbeck Laboratory is equipped technically and with staff to facilitate translation of new management strategies into the clinic.
Identification of biomarkers for clinical management of bladder, renal and prostate cancer
For bladder we use a combined approach, screening for:
- Aberrations at the genomic level with array-based comparative genomic hybridization in cooperation with Associate Professor T. Díaz de Ståhl, Experimentell patologi at the Rudbeck Laboratory, in Uppsala.
- Changes in protein expression using antibodies, assessed by immuno– histochemistry on tissue microarrays and serum in collaboration with Professor Fredrik Ponten from the Swedish Human Proteome Resource project group (HPR) at the Rudbeck Laboratory.
- High resolving mass spectrometry (MS) to study the urinary proteome of patients with bladder cancer with Professor U. Pettersson, IGP.
- Genetic and epigenetic profiling in cooperation with researchers at Johns Hopkins University in Baltimore, USA.
The series of samples to be included in the study represent a large unique material collected in our biobank. It is important to remark that, candidate markers will be finally validated in an independent collection of tumor samples within the Nordic trial database (chairman Per-Uno Malmström) but also through our EU collaborative project (UROMOL). The later prospective project has the aim to find urinary markers for outcome of bladder tumors. We have established a multi-disciplinary collaboration between our department and Pathology and Physical and Analytical Chemistry to search for novel biomarkers for prostate cancer progression. In this collaboration where proteomic analyses of prostate cancer tissues have been performed a number of potential, novel biomarkers have been identified. These novel candidates might be useful in prostate cancer diagnosis to predict prognosis for the individual men, but their possible use in the future has to be further evaluated. In renal cancer 362 patients with serum samples collected between 1983 and 1998 have been analyzed regarding clinical follow up and a search for biomarkers have been initiated with researchers at KTH Stockholm.
Concerning experimental therapy we collaborate with the Division of Biomedical Radiation Sciences to develop nucleide based tumor targeting (PI Truls Gårdmark). The aim of the research is to develop new methods for treatment of tumours, especially such tumours that have a tendency to cause metastases. The present project is preclinical but the developed substances are made available for clinical tests when relevant. One clinical trial with AFFIBODY® in cooperation with industry is planned to start in the near future.
In collaboration with the Department of Clinical Immunology projects have been initiated to develop tumor vaccines. In bladder a model for immunostimulating gene therapy has been initiated and we have identified a promising vector, CD40L for clinical trials. A phase 1 trial has been completed and a manuscript submitted.