Abstract PL03-01: Evolutionary dynamics of cancer in response to targeted therapy

Abstract

Abstract Cancer is an evolutionary process. Cancer initiation and progression are caused by somatic mutation and selection of dividing cells. The mathematical theory of evolution can therefore provide quantitative insights into human cancer. I will discuss the role of chromosomal instability (CIN) and the accumulation of drivers and passengers in growing tumors. I will study success and failure of targeted therapy including combination of different drugs and evolution of resistance. A simple conclusion is that combination treatment can succeed, if the cancer requires at least two point mutations to gain resistance. From the perspective of preventing resistance, simultaneous therapy is highly recommended whereas sequential therapy is a recipe for almost certain treatment failure. Further Reading 1. Bozic et al (2010). Accumulation of driver and passenger mutations during tumor progression. Proc Natl Acad Sci USA 107: 18545-18550. 2. Diaz et al (2012) The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486: 537-540. 3. Bozic et al (2013). Evolutionary dynamics of cancer in response to targeted combination therapy. eLife 2: e00747. Citation Format: Martin Nowak. Evolutionary dynamics of cancer in response to targeted therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr PL03-01. doi:10.1158/1538-7445.AM2014-PL03-01