Tumor Composition and the Host Environment on Cancer Treatment Strategies

The one-size-fits-all approach is not effective at treating cancer and tumor heterogeneity plays an important role in patient response. Current dogma characterizes tumor heterogeneity resulting from compounding genetic and epigenetic changes and instability, ultimately driving unfavorable outcomes for these patients. However, some cancers, including many pediatric cancers and some leukemias, have limited genomic diversity. As a result, we have a limited ability to stratify patients into high versus low-risk groups. To address this, we explore intratumor heterogeneity across a variety of different tumor types to quantify and identify driving phenotypes in tumor evolution. We leverage the generalized diversity index (GDI) from ecology, which allows us to tailor the scale of cellular diversity in a given context. We can tune GDI to either emphasize clonal richness versus shifting the analysis toward the abundance of potential drivers of the tumor evolution. Further, these approaches, in combination with mathematical modeling, can be used to develop new adaptive therapeutic strategies that leverage information about the host environment for gaining better control over cancer growth.