The Physics of Cancer Metastasis Meeting to be held in Arlington, VA on Nov. 1-2, 2010 will discuss the prospects for defining a set of short term (3-5 year) projects, which could be successful in leading the way to deeper understanding of the fundamentals of the metastatic process and possibly to radical new treatment ideas. The discussion will be held between leading cancer researchers and leading physicists working at the interface of biology and physics. The physics community working at the physics-biology interface is excited by the possibility of contributing to the fundamental understanding of cancer, which is a failure of multi-cellularity, but is also an essential byproduct of evolution. The meeting is sponsored by the Physics Division at NSF.
PHYSICS OF CANCER METASTASIS (Conference) PHYSICS OF CANCER METASTASIS Approximately thirty scientists, equally divided between cancer biologists and physical scientists, met for a day and a half at a meeting sponsored by the NSF Physics of Living System Program. The scientific focus of this meeting was the subject of cancer metastasis, as it is the spread of cancer cells from a primary tumor to secondary sites, and their subsequent growth at those sites that results in patient mortality. The overall goal of the workshop was to begin a dialogue on possible contributions to understanding metastasis that can be made by taking advantage of advances in both experimental physics and in the theory of living processes, and to discuss possible organizational strategies for enabling those advances. The program of the meeting was divided into three parts: presentations by cancer biologists, presentations by physical scientists, and open discussion of the issues at hand. The formal presentations by the cancer researchers established various concepts regarding metastasis that set the stage for future progress. Given the need for progress along multiple lines, there appear to be several avenues along which physical science can play an important role. These break down into possible advances in local sensors, advanced imaging modalities (and model systems), and theoretical studies. Local sensors could detect elements that are beginning to play a prominent role in various conceptual frameworks concerning tumor progression. For example, mechanical stresses on individual cells (to be distinguished from hydrostatic pressure in the tumor) could be directly coupled to gene expression, growth rate and apoptotic probability. A recent example (see Grashoff, C. et al. Nature 466, 263–266 (2010). of a force sensor that has yet to be applied in the cancer context is based on vinculin, a cytoskeletal-associated protein involved in cell-matrix adhesion. This particular example may turn out to be not suitable, but the principle that one can design clever molecular probes to report on and eventually actively modulate cell states is one that could be applied fruitfully to the problem of metastasis. Note though that measurements are much more useful if they can be interpreted in the light of a useful theoretical model. Quite a bit of the discussion dealt with the role of theory and modeling, as this was clearly a missing component in many of the methods that were being pursued in this field. It is perhaps useful to consider different types of theoretical treatments and methodologies. The systems biology approach aims to create bottom-up models of extremely intricate signaling pathways and intercellular interactions. For cases in which this can be reliably accomplished (we heard for example about successes in using this level of modeling for bacterial chemotaxis), this is obviously the most quantitatively useful approach. It is fair to say, though, that we are very far from this regime for any cancer problem. Of more use here are conceptual theories such as the one described by Geoff West on scaling related to transport needs and the one briefly alluded to earlier about the role of homeostatic stress on the competition between normal and neoplastic tissue. Other questions that could be investigated in this manner include the epithelial-mesenchymal transition (and the reverse mesenchymal to epithelial transition in the secondary tumor), the formation and structure of the tumor vasculature (coupled to experimental measurements of the same), the effects of blood flow shear on cancer cell survival and the role of stochasticity in overcoming metastatic inefficiency. This type of theory can be very useful in conjunction with a coupled experimental program, since it offers guidance as to most informative things that one can measure as predictors of future progression and possibly even response to treatment. In this regard, there was some debate about whether ecological paradigms (dispersal theory as a way of understanding selection for motile mutants, for example) could serve a useful purpose here. It is reasonable to hypothesize that we will not really be able to learn much from the vast amounts of genomic data becoming available without sophisticated evolutionary theories; some of this work is already beginning. Cancer touches on some of the most basic questions underlying biology, related to the plasticity of genetic degrees of freedom, the nature of cell differentiation, the constraints that multi-cellularity places on the proliferation and selfish behavior of individual cells, the role of environment in both genotypic selection and phenotypic behavior etc. . Clearly, the community will be grappling with these overarching issues for many decades to come. However, this should not preclude the possibility that many smaller scale issues can be addressed with modern methods and that one could imagine projects with 3-5 year lifetimes that could positively impact both our understanding and our clinical practice.
