biocare2-logo.gif Biomarkers in Cancer Medicine


Executive Summary

The Lund University (LU) and University of Gothenburg (UGOT) cancer program, BioCARE, will based on cutting-edge omics platforms, extensive biobanks, close multi-disciplinary collaboration between senior cancer researchers from two universities and three university hospitals and the identification and analysis of biomarkers and their complex networks, have a major impact on the way cancer is diagnosed, treated and managed in the coming 5-10 years. BioCARE presents a program for identification and clinical exploitation of biomarkers in cancer medicine. Modeled on the first translational cancer center in Sweden, CREATE Health, with a proven track record of identifying clinical relevant cancer biomarkers, BioCARE will obtain a jump start, unique to large program proposal. Biomarkers are crucial tools to diagnose and stage disease types, predicting outcome of different therapeutics, as well as monitoring pharmaceutical development. Focusing on a limited number of tumors, where presently both biomarker and clinical research is strong, our ambitious goals include the identification and validation of biomarkers both as diagnostic and therapeutic targets and identification of cancer subpopulations based on clinical behavior and treatment response in tumors.

The overall aim is to introduce "personalized medicine" when handling cancer patients, a development strongly supported by pharmaceutical and biotech industry, and to find means to select those patients benefitting from current treatment protocols and thereby maximizing the effect for the patients, as well as minimizing the cost for the health care system.

Our mid to long-term visions are:

1) To develop novel diagnostic and prognostic biomarkers to further sub-stratify patients likely to respond to current or novel treatments

2) To be able to predict which patients will develop treatment resistance and relapse of tumor.

3) To be able to test a limited set of novel therapeutic targets in Phase I/IIa clinical trials, using in-house Clinical Research Units

4) In collaboration with pharmaceutical companies, to initiate the development of clinically useful cancer drugs

Background

In a recent report by Klevmarken and Lindgren (2008) the estimated future cost for healthcare, with a steadily ageing population, will increase by 270 % over the next 3 decades. Today 17 % of the population is 65 years or older but by year 2040 this group will constitute 24 %. The cost for healthcare would then constitute 36 % of the total tax income, compared to 20 % today. Even if this high figure is to pessimistic it nevertheless indicates that the cost of health care in the years ahead will impose a considerable strain on society. Thus, serious efforts must be made to improve the way we detect and treat the most prevalent diseases. The incidence of cancer increases with age, and thus the clinical management of cancer is a major challenge for the 21st century. The cost of cancer treatment has increased dramatically in recent years, partly due to the use of novel biological drugs. Despite new drugs and recent advances in understanding the molecular pathogenesis of the disease mortality figures remain high. Therefore it is of outmost importance to identify new strategies for the management and treatment of cancer disease and the consensus is that biomarkers will have the necessary power to significantly contribute to such a development.

Biology - the challenge

Cancer is a multigenic and multicellular disease that can arise from virtually all cell types and organs. At the molecular level it affects all aspects of cellular life e.g. survival, cell division, differentiation and migration and at the systemic level it co-opts and mimics developmental programs, such as angiogenesis, lymphangiogenesis, stromal organization, and organ formation. Multiple genes and cellular pathways can be affected and there is a considerable genetic and epigenetic variability even within a specific subtype of tumor. These facts, together with the tumor stem cell concept, provide explanations for the tremendous phenotypic heterogeneity observed in most malignancies as well as the shortcomings in establishing efficient treatment protocols for aggressive tumor forms. In the clinical setting the complexity of cancer behavior is not only determined by tumor cells proper, but aggressiveness is also affected by the interplay between tumor cells and immune, stromal and blood vessel cells, which most profoundly determine tumor behavior. Thus, future refined treatment strategies have to take into account the geno- and phenotypic heterogeneity leading to cellular diversity and escape from current treatment protocols.

Strategic Infrastructures

In 2000 LU and UGOT together with Chalmers University of Technology established the Wallenberg-funded post genomic Swegene consortium of functional genomics. Swegene established a number of technology platforms with world-leading omics technologies and instrumentations. These platforms have been very successful in technology development, bioinformatics and systems biology. In Lund the most successful Swegene technology platforms have been brought together in a Center for Integrative Biology (SCIBLU) sponsored by LU and in UGOT they are now operating within the Core Facility organization. This, and other consistent and systematic investments in technology for high-throughput analyses of biological samples by the two universities have resulted in advanced technical infrastructures such as CREATE Health, Bioimaging Center (Lund), the Tissue Microarray Unit (Malmö), and Centers for Specialized Care in Oncology (Lund and Gothenburg), aiming at refined diagnosis and novel therapeutic initiatives for the benefit of cancer patients. The extensive biobanks available in Malmö, Lund and Gothenburg will allow us to verify the specificity and clinical usefulness of the identified biomarkers. Moreover, the Tissue Microarray Unit harbours several large diseasespecific, clinically well-annotated sample banks, representing all major cancer forms and is today already closely linked to CREATE Health. The tissue microarray facility will add the necessary expertise to evaluate the clinical usefulness of our biomarkers. In addition, clinical diagnostic platforms at the LU/UGOT Departments of Laboratory Medicine will enable rapid translation of clinically relevant biomarkers into accredited laboratories, thereby providing quality-assured service for the two health-care regions. In brief, these infrastructures will serve as a strong and necessary technology base when bridging the basic/applied and clinical research areas within BioCARE.

Research Organization

The knowledge and competence of cancer research groups at LU/UGOT focusing on cancer biomarkers constitute a tremendous asset and will be organized to facilitate exchange of ideas, know-how and techniques. A director well accustomed with the organization and running of large, multi-disciplinary research collaborations, will head the program. Professional administrative, as well as financial, expertise will be brought in as supporting resources, which from previous experience is considered an absolute necessity. One of the means by which we will foster direct contacts and flow of know-how, will be a jointly run Research School and Academy for Young Scientists. Furthermore, strategic innovation issues will be a major focus, strongly supported by the university management, which is a prerequisite for a successful implementation of novel diagnostic and therapeutic biomarkers into a routine clinical environment.

BioCARE is a globally competitive initiative that builds on major, long-term investment by LU/UGOT together with external funding bodies. We see the program as a forceful investment for implementing our cancer research and innovation strategies and anticipate that the proposal will have the highest scientific and technological impact and consequently be of immediate strategic importance to both industry and health care (see Letters of Support).

Read the application in its full length.

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BioCARE Lund University - Medicon Village 406 (311K2), Scheelevägen 2 - SE-223 81 Lund - +46-46-2226420

BioCARE University of Gothenburg - Cancer Center Sahlgrenska - Box 425 - 405 30 Göteborg -

Email BioCARE - www.biocare.nu

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