NTTS 2017

Neoplasms change over time, metastasize and ultimately lead to patient death, through a process of cell-level evolution. This process is driven by genetic and epigenetic alterations. However, the ecology of a neoplastic cell’s microenvironment determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date no system has been proposed for drawing clinically relevant distinctions between how different tumors are evolving. We lack a language with which to communicate and coordinate about the dynamcis and trajectories of cancers. We propose a framework for classifying tumors that is based on four relevant components: (1) diversity of neoplastic cells (intra-tumor heterogeneity) and (2) changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the (3) hazards to neoplastic cell survival, and (4) resources available to neoplastic cells, which make up an ecological index (Eco-index). Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient’s tumor. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research.