Nature Reviews Cancer | AOP, published online 10 September FOCUS 2010; doi:10.1038/nrc2913 ON CANCER PROTEOMICS Nature Reviews Cancer | AOP, published online 12 August 2010; doi:10.1038/nrc2913 PERSPECTIVES it is now clear that much larger biobanks are SCIENCE AND SOCIETY required7,8. For genetic main-effect studies 2,000–5,000 samples are needed, for lifestyle Integrating biobanks: addressing the main-effect studies 2,000–20,000 samples are required and for gene–lifestyle interaction practical and ethical issues to deliver studies 20,000–50,000 samples are required8. Only when these larger resources are availa- ble can we truly understand the interactions a valuable tool for cancer research between gene, environment, lifestyle and disease and translate this knowledge into the R. William G. Watson, Elaine W. Kay and David Smith clinic through innovative diagnostics, thera- peutics and preventive strategies for cancer. Abstract | Cancer is caused by complex interactions between genes, environment These larger resources can only be achieved and lifestyles. Biobanks of well-annotated human tissues are an important resource by the integration of existing biobanks that for studying the underlying mechanisms of cancer. Although such biobanks exist, already have a wealth of information and their integration to form larger biobanks is now required to provide the diversity samples. However, there are many obstacles of samples that are needed to study the complexity and heterogeneity of cancer. and challenges associated with such integra- tion, including technical, logistical, ethical Clear guidelines and policies are also required to address the challenges of and legal ones. integrating individual institutional or national biobanks and build public trust. This Groups across both North America and Science and Society article highlights some of the main practical and ethical issues Europe have started to address these obsta- that are undergoing discussion in the integration of tissue biobanks for cancer. cles and challenges to move this process forwards. Initially, national programmes It is widely accepted that although basic The potential benefits of this personalized were established that linked previously col- scientific studies carried out using cell lines approach to the treatment of disease are lected biobank samples. These included and animal models can be informative considerable. They include the identifica- the Canadian Tumour Repository Network about the cellular and molecular aspects tion of improved biological targets using (CTRNet; see the CTRNet website; Further of cancer there is a clear requirement to validated biomarker studies, the capacity to information), which was established to link confirm this in human samples. The con- increase the likely success of clinical trials by cancer researchers with provincial tumour cept of patient-specific and disease-specific preselecting the patient population and the banks, thus creating new opportunities for (‘targeted’) therapy has expanded rapidly in fact that this will in turn reduce the time, cost translational cancer research to improve can- recent years. Many researchers believe that and the likelihood of failure of clinical trials4. cer outcomes in Canada and beyond. This this concept of personalized medicine will Information from validated biomarker stud- network gave researchers access to tissue and provide the solution to the considerable ies also allows the re-introduction of drugs clinical data. The Organisation of European challenges posed to the clinical treatment that have failed in a clinical trial setting Cancer Institutes (OECI) TuBaFrost database of cancer. The move from the traditional or that have been withdrawn from the mar- (see the TuBaFrost website; Further infor- ‘one size fits all’ approach for the treatment ket to be re-applied in a more targeted way. mation) was established in 2003 to network of cancer to targeted approaches seems to Similarly, biomarker studies might also offer European frozen tissue pathology banks for offer genuine hope for improved patient the potential to avoid adverse side effects, cancer research. In this initiative, the tis- outcomes. There are a few examples for and this would, in turn, lead to higher sue collection process was standardized, a which the concept of a highly effective compliance with various treatment regimes. code of conduct for the exchange of residual drug treatment targeted towards a specific human material for research was developed limited patient population has become The need for large integrated biobanks based on European legislation and a web- reality. The use of imatinib (Gleevec; One of the biggest limiting factors to the suc- based sample request process was developed. Norvartis) in chronic myeloid leukaemia1, cessful translation of basic scientific cellular Other examples include the Spanish tumour the use of monoclonal antibodies that tar- and molecular studies into improved patient bank, EuroBoNet (see the EuroBoNet web- get the epidermal growth factor receptor outcome has been the lack of access to large, site; Further information) and the Office of (EGFR) in patients with EGFR-expressing appropriate and well-annotated cohorts of Biorepositories and Biospecimen Research metastatic colon cancer2 and the use human tissue5,6. Focused disease-specific (OBBR; see the OBBR website; Further infor- of the ERBB2 (also known as HER2)- institutional biobanks have had some success mation) in the USA. These initial biobanks specific monoclonal antibody trastuzumab in translational and personalized medicine led to further expansions and networking (Herceptin; Genentech) in ERBB2-positive (as described above). However, owing to the to create resources across Europe and the breast cancers3 are such examples. complex and heterogeneous nature of cancer, United States. The establishment of the NATURE REVIEWS | CANCER ADVANCE ONLINE PUBLICATION | 1 © 2010 Macmillan Publishers Limited. All rights reserved PERSPECTIVES European Biobanking and Biomolecular Box 1 | The Biobanking and Biomolecular Resources Research Infrastructure Resources Research Infrastructure (BBMRI) programme (see the BBMRI website; Further The European project Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) was established in 2008 to network European biobanks with the aim of improving resources for information) illustrates moves to coordi- biomedical research and therefore contributing to the improved prevention, diagnosis and nate existing biobanking activities across treatment of disease. The resource includes 261 biobanks across 23 countries with a total of more 9,10 Europe (BOX 1). The development of the than 16 million samples. It is only possible to achieve this using a federated network of centres in Cancer Bioinformatics Grid (caBIG®) infra- European countries, which is best described as a distributed hub structure of existing biobanks. structure (see the Cancer Bioinformatics This will provide the flexibility to facilitate expansion and multiple uses (see the BBMRI website; Grid website; Further information) is Further information). connecting research organizations across The mission of the BBMRI is: the United States11 (BOX 2). The National • To benefit European health care, medical research and, ultimately, the health of the citizens of Comprehensive Cancer Network (NCCN; the European Union see the NCCN website; Further information) • To have a sustainable legal and financial conceptual framework for a pan-European Biobank has collected patient data outcomes for infrastructure breast cancer, non-small-cell lung cancer, • To increase scientific excellence and efficacy of European research in the life sciences, especially colorectal cancer, non-Hodgkin’s lymphoma in biomedical research and ovarian cancer. The data, along with • To expand and secure the competitiveness of European research and industry in a global records of patient treatments and patient out- context, especially in the fields of medicine and biology comes, have allowed retrospective compara- tive studies to be conducted. The analysis of subpopulations in these databases has already However, providing a clear definition of the Epidemiological Research (DataSHaPER; led to changes in clinical practice12,13. scope of a biobank is a problem when inte- see the DataSHaPER website; Further There are many reports outlining the grating biobanks that have been collected information) has been developed through complexity of biobanking that provide across different institutions or countries for the Public Population Project in Genomics strong recommendations and the identifica- different reasons. There is a clear need for (P3G) and Promoting Harmonisation tion of best practice for all aspects of the such flexibility, owing to the ever-expanding of Epidemiological Biobanks in Europe process14 (see the National Cancer Institute development of technology and under- (PHOEBE) and involves 25 international Best Practices for Biospecimen Resources standing of the complexity of cancer, but biobanks. These international collabora- website; Further information). FIGURE 1 out- this flexibility has effects on patient consent, tions have defined several core high priori- lines the steps involved in biobanks. As the standard operating procedures, information ties for improved study integration, such as requirements for complex multi-institutional technology management systems, and the sample collection, preliminary processing and international collections to study cancer