Mechanisms in Cancer Evolution Program

The Mechanisms in Cancer Evolution Program at the DLDCCC is focused on understanding molecular mechanisms that generate heterogeneity (genetic and non-genetic or epi-genetic) and environmental drivers that spur evolution of cancers. Evolution occurs by variation, which creates heterogeneity and selection. Heterogeneity is generated by intrinsic genomic and non-genetic phenotype-plasticity mechanisms, as well as by alteration of cellular programs by extrinsic viruses, the microbiome, and nutritional modulation. The goal of the program is fundamental basic science discovery of how these molecular mechanisms work. New paradigms discovered can open new translational directions (throughout the DLDCCC Programs and by others), including novel evolutionary biomarkers, diagnostic, preventative, and therapeutic tools. For example, whereas conventional therapies kill cells or stop them from growing (are anti-proliferative), proposed novel interventions that would slow evolution, promise new and fundamentally different ways to inhibit oncogenesis and thwart resistance. Also, identification of biomarkers of highly evolvable cells may allow detection of at-risk individuals, and earlier detection of cancers.

The two program aims encompass mechanisms of promotion of heterogeneity by:

• Intrinsic Evolution Promoters (mutation, genome rearrangement, recombination, epigenetic heritable protein- and RNA-error-mediated variation)
• Extrinsic Evolution Promoters, including viruses, microbes generally, the microbiome, and nutritional modulators of both host and microbiome

The NCI Cancer Center Support Grant supports this Research Program by providing key Shared Resources, particularly High-Parameter Flow Cytometry; Advanced Microscopy and Image Informatics; Genomic, Transcriptomic, Epigenomic and Single-Cell, Metabolomics, and Proteomics; as well as administrative support for meetings, clubs and interest groups, and pilot funding and recruitment funds.