How combining an evolutionary perspective with genomic methods can advance CLL treatment

Dan Landau, MD, PhD of Weill Cornell Medical College and the NYGC, New York, NY gives an overview of his talk on clonal evolution in chronic lymphocytic leukemia (CLL) held at the 2016 International Workshop of the German CLL Study Group (GCLLSG) in Cologne, Germany. Dr Landau explains that we understand that a malignant population such as a population of CLL cells in any patient, is actually not uniform but composed of multiple sub-populations, which continuously compete, evolve and create diversity. The therapeutic challenge is that in each patient, we are not dealing with one disease but with a collection of many diseases. Therefore, it is not surprising that therapies can fail. With new genomic technologies, it is now possible to survey this genetic complexity for large cohorts of patients in order to understand the processes underlying the complexity. By taking an evolutionary perspective and combining it with genomic methods, we can infer the past history of disease and use this information to predict its future. Dr Landau points out how today data science approaches are already being used to predict real world outcomes in advertising or on the stock market for example. However, data science approaches are not really being applied in cancer research. Further, he discusses non-genetic sources of diversity, such as epigenetics and spatial location. All of these layers of information need to be considered in order to understand the evolutionary process. Finally, he discusses the idea of measuring clonal kinetics directly in patients, i.e. measuring the rate of growth of each clone with each therapy and come up with an optimized therapeutic approach through the use of algorithms; he considers this approach to be a radical extension of the precision medicine paradigm.

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