Principal Investigator Leonid Mirny
As a part of a recently formed, NCI-funded center for Physics-in-Oncology, we developed a program in evolutionary dynamics of cancer. By considering neoplastic progression as a micro-evolutionary process we study accumulation of driver and passenger mutations in cancer. While the former are responsible for cancer progression and are in the spotlight of studies in oncology, the later may confer deleterious to cancer cells -- a vulnerability that can be exploited by therapeutics. By combining simulations of cancer progression with analysis of cancer genomic data we developed methods to characterize patterns of mutations in cancer, allowing to differentiate tumor suppressors from oncogenes, and passengers from drivers. We measured fitness effect of different classes of mutations demonstrating that passengers are subject of weakened purifying selection and are likely deleterious to cancer cells.The goal is to develop a theory of neoplastic evolution informed by cancer genomic and experimental data; use it as a framework for characterization of driver and passenger mutations by original statistical techniques, and to test feasibility of pushing a cancer into a population meltdown due to elevated mutation load.