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Discovery Sciences Emerging Scholars Lecture series presents Leonard Alfredo Harris, Vanderbilt University: "Bet Hedging as a Survival Strategy in Complex Biological Systems and Cancer.”
Cells are complex, dynamic systems capable of initiating internal biochemical programs and adjusting their behavior in response to microenvironmental signals and stressors. Under the general term “phenotypic plasticity,” this phenomenon underlies important biological processes such as stem cell differentiation and epithelial-to-mesenchymal transitions. In bacteria, isogenic cell populations are known to exploit plasticity by phenotypically diversifying to increase their chances of survival to catastrophic external challenges, a strategy known as “bet hedging.” Recent evidence suggests that cancer cells may employ a similar strategy to survive the initial onslaught of anticancer therapeutics. Understanding the complex biochemical networks that underlie signal propagation and cell fate decisions is thus critical for improving treatments of various human diseases, including cancer. Here, I describe the biochemical basis for phenotypic plasticity within the framework of “Waddington landscapes,” present evidence for its role in anticancer drug resistance in non-small cell lung cancer and melanoma populations treated with targeted drugs, and discuss initial work toward constructing a detailed computational model of the biochemical machinery underlying cellular responses to external perturbations.