Seed Grant in Cancer and Evolution
PIs are Jason Somarelli and Will Eward, Duke. Cancer represents a breakdown of normal tissue maintenance in which cells acquire the ability to grow uncontrolled. This uncontrolled growth is often treated with surgery, followed by chemotherapy and/or radiation. In many cases, these treatments significantly prolong life and can even lead to cures in some cancer types. However, some cancer cells that are treated with chemotherapy/radiation acquire additional alterations that enable them to become resistant. The emergence of drug/radiation-resistant cells is governed by evolutionary forces of natural selection and survival of the fittest. In the presence of the therapy, resistant cells have a fitness advantage over sensitive cells. As the sensitive cells die off in response to treatment, the resistant cells emerge and begin to take over the population. Interestingly, however, the resistant cells are often less fit than the treatment-sensitive cells when the treatment is removed. We hypothesize that these differences in fitness can be exploited to control the relative populations of treatment-sensitive and treatment-resistant cells during cancer growth. To test this hypothesis, we will use experimental data and phylogenetic analyses of publically-available data to determine whether we can take advantage of the differences in fitness between these cell types to better control tumor growth and further prolong survival.
Jolly MK, Ware KE, Xu S, et al. (2019). E-cadherin represses anchorage-independent growth in sarcomas through both signaling and mechanical mechanisms. Molecular Cancer Research 17(6): 1391-1402.
Xu S, Ware KE, Ding Y, et al. (2019). An integrative systems biology and experimental approach identifies convergence of epithelial plasticity, metabolism, and autophagy to promote chemoresistance. Journal of Clinical Medicine 8(2): 205.
Somarelli JA, Gardner H, Cannataro VL, et al. (2020). Molecular biology and evolution of cancer: From discovery to action. Molecular Biology and Evolution 37(2): 320-326.