The US-Japan International Cancer Systems Biology Meeting was held October 28-29 at the RIKEN Yokohama Institute. The event was hosted by the US National Cancer Institute, The Systems Biology Institute, RIKEN RCAI, and the Japanese Foundation for Cancer Research. The goals of the meeting were threefold: 1) to bring together leading experts in systems biology and cancer to exchange current state-of-the-art research, 2) to identify challenges and barriers that may be inhibiting progress in the field, in particular in terms of bringing current knowledge into the clinic, and 3) to identify opportunities for interactions and collaborations at the individual and institutional levels.
Cancer is an ideal, albeit difficult, target for the systems biology approach. It has long been known that cancer is a complex disease and it is becoming more appreciated that there is considerable heterogeneity even in an individual patient, both within the tumor and over time. The talks at the meeting were very diverse, but there were common themes and issues. Much of the deep analysis of cancer as a system is of cell lines rather than primary tumor cells. The potential pitfalls of this approach have long been recognized by reductionist biologists and are appreciated by systems biologists as well. Nonetheless, cell lines are invaluable as a starting point; knowledge gained from cell line studies can provide the foundation for subsequent ex vivo analyses of primary cells. A point made by several speakers is the importance of having a common repository of cancer cell lines so that all researchers in the field are applying systems biology tools to as uniform a starting population as possible. Such cell line panels are currently maintained in the US by the NCI (NCI60) and in Japan by the Japanese Foundation for Cancer Research (JFCR39). However, the participants were in agreement that having one central source of single-cell-derived, well-characterized, clonal cell lines would be highly desirable.
One of the goals of systems biology as it relates to cancer is to develop personalized cancer therapy. It is now possible to screen patients for mutations/amplifications in known oncogenes and tumor suppressor genes, and this information can sometimes provide an initial rational approach to appropriate therapy. However, as pointed out by several speakers, typically only a fraction of patients categorized in this way will respond to a given therapy. The genetic complexity of individual tumors and the existence of multiple different additional mutations clearly play a role in treatment failures, and ferreting out this type of higher order information is within the realm of the systems biologist. Although not yet possible, the goal is to be able to provide patients with a profile of their cancer that will allow for effective therapy. The development of tools to accomplish this is a major challenge for systems biology.
One presentation that generated considerable discussion was by Stephen Friend (Photo) of Sage Bionetworks. He predicted that as the tools now in use develop, there will be a ten-fold increase in data generation, and that the systems biology community is unprepared to handle this data explosion. He pointed out that taking individual network approaches, e.g. transcriptome, metabolome, etc., even as complex as these each are, is insufficient for making progress against cancer and other diseases, and that a mechanism is needed to link all data sets together. Although there seemed to be general agreement on the value of this approach, many issues still remain, for example patient privacy regulations and the lack of electronic medical records in many hospitals, making any "omics" data incomplete and sometimes useless if it cannot be tracked back to clinical outcomes. Other concerns include intellectual property rights, which might preclude some investigators, often at the insistence of their institutional guidelines, from submitting data to such a repository, as well as a more general problem, allocation of credit to individuals in an area that is of necessity big Team Science.
Clearly systems biology has great potential yet is experiencing some growing pains. The Yokohama participants agreed that meetings such as this one were very fruitful, as scientists wrestle with complex and sometimes thorny issues.