Conveners
The cancer ecosystem: optimizing treatment based on evolution
- Jill Gallaher (H. Lee Moffitt Cancer Center)
- Alexander R. A. Anderson (Moffitt Cancer Center)
Description
Tumours are not simply collections of mutated cells that grow in isolation of the environment in which they live. They interact with and modify both the physical microenvironment and a variety of nontumor cells that make up the organ in which the cancer originated. In nature, ecology and evolution are intimately linked since one provides the players and the other provides the field. The idea of viewing cancer from an ecological perspective fundamentally means that we cannot just consider cancer as a collection of mutated cells but rather a dynamic system of many interacting cellular and microenvironmental elements. Heterogeneity is both a cause and consequence of the interaction between the tumour and its environment and has been observed across genotypic, phenotypic, and environmental scales and has now been recognized as a key driver in cancer drug resistance and treatment failure.
Importantly this complex dialogue is governed by Darwinian dynamics, i.e. local microenvironmental conditions select phenotypic tumour clones that are best adapted to locally survive and proliferate. Conversely, the phenotypic properties of the cells (through release of growth factors or metabolites) affect the environmental properties. While these complex interactions have enormous clinical implications because they promote resistance to therapy, they rarely incorporated into clinical design. In fact, many treatment approaches only focus on specific molecular targets without considering the context or consequence.
In this minisymposium, we present ecological and evolutionary perspectives on cancer progression and treatment. By combining models with biological or clinical data, progression can be better understood and novel treatment strategies can be designed based on ecological and evolutionary principles.
Evolutionary game theory has been used to model cancer for more than a decade. Efforts to date have focused on understanding the effect of interactions between cancer cells of different types, and between aspects of the tumour microenvironment and cancer cells. To realise the full potential of these modelling efforts however, we submit that a method for direct parameterisation is required. In...
Several types of cancer initiate or metastasize to the bone. These include the most prevalent and lethal cancers: lung, breast and prostate. Thus understanding the bone ecosystem is key if we want to predict what phenotypes will successfully metastasize to the bone and the subsequent evolutionary dynamics that will ensue as the invading tumour cells learn how to co-opt the bone resident cells....
Glioblastoma is the most aggressive primary brain cancer, with poor survival that can be largely attributed to intra-tumoural heterogeneity. While these tumours are primarily monitored via contrast-enhanced (CE) T1-weighted and T2-weighted magnetic resonance (MR) images, these standard clinical images are known to be non-specific in their correlation with tumour cell density. This lack of...
Tumours consist of a hierarchical population of cells that differ in their phenotype and genotype. This hierarchical organization of cells means that a few clones (i.e., cells and several generations of offspring) are abundant while most are rare, which is called clonal dominance. Such dominance also occurred in published in vitro iterated growth and passage experiments with tumour cells in...