Alexander Anderson

• 
  It's not just genes: how interactions drive cancer progression
  Alexander Anderson
  No description available.
• 
  The Role of Heterogeneity in Cancer Progression and Treatment Failure
  Alexander Anderson

  Heterogeneity in cancer is an observed fact, both genetically and phenotypically. Intercellular variation is seen at all scales and stages of development, and has significant implications for prognosis. At present, our understanding of this heterogeneity is mainly restricted to the genetic scale with little information regarding the relationship between genetic and phenotypic heterogeneity. Further, little is known about how cells alter their microenvironment or how these changes drive selection and feedback to further drive cancer evolution.

  
  

  Strong selective pressures imposed by a milieu of microenvironmental factors combined with high profileration rates and high mutation rates inevitably lead to the rapid emergence of resistance to therapy. Hence, the failure of cancer therapies is often attributed to Darwinian evolution. To understand and predict cancer evolution we must understand not only the mutations which drive evolution but also the mechanisms through which these mutations manifest themselves in phenotypic change. Thus, our success in predicting cancer progression and designing effective therapy is contingent on understanding the junction at which genes and environment meet to produce phenotypes, the genotype-phenotype (GP) map.

  
  

  Experimental studies have revealed the complexity inherent within the GP-map which is responsible for the difficulty in predicting evolution; many genotypes produce identical phenotypes and further many phenotypes can emerge from a single phenotype. Indeed, recent experimental evidence shows that this mapping produces phenotypic heterogeneity through a variety of genetic and non--genetic mechanisms. Heterogeneity can be driven through phenotypic plasticity, the phenomenon whereby isogenic cells in different environments display different phenotypes. Further, isogenic cells in identical environments can display phenotypic heterogeneity which is the manifestation of intra--cellular noise amplified through the complex machinery of the cell signalling pathways. In this talk I will present a collection of related mathematical models which explore genetic, environmental, phenotypic and morphological heterogeneity through the unifying lens of the GP-map, outline the key mechanisms which could be responsible for generating adaptive phenotypes -- mutation, plasticity and stochasticity -- and explore the implications of these mechanisms for developing novel and effective cancer therapies.