Cancer cells compete for resources among each other and with the normal cells in the body. Therefore, a limited supply of resources and metabolic constraints suggest trade-offs that exert selective pressures. Experiments in breast cancer cells have shown a reduction in proliferation rates when detoxifying oxygen species. Similar trade-offs between the metabolism of serine and glutamine have been observed in estrogen-positive versus negative cells. Aktipis and colleagues provided a perspective on applying life-history theory to the evolution of cancer. In particular, they posited that different hallmarks of cancer associate with faster or slower life histories depending on the stability and availability of resources in the microenvironment.
Thinking along these lines, I am trying to develop and test several hypotheses.
- If trade-offs occur between the different tasks performed by cancer cells, specialization would also be possible. A few studies have shown that this is the case using gene expression data. In particular, I am trying to test one explicit prediction of this model, namely that specialist cells would be particularly susceptible to drugs that perturb their tasks.
- Once established, task specialization can be used to explore and explain some of the behaviors of cancer cells. In particular, I am trying to use cell specialization to explain the disparity of gene expression and protein levels.
- Reviewing and synthesizing evidence of cancer cell specialization and task trade-offs with emphasis on the implications for understanding the behavior of cancer and potential applications for treatments.
Disruption of cancer cell functions by task-specific drug perturbations
Mahmoud Ahmed, Deok Ryong Kim
Frontiers in Pharmacology, vol. 13, 2022