Activity: Talk or presentation (speaker at event) › Talk or presentation › Academic
While systemic therapy for disseminated cancer is often initially successful, malignant cells, using diverse adaptive strategies encoded in the human genome, almost invariably evolve resistance, leading to treatment failure. Thus, the Darwinian dynamics of resistance are formidable barriers to all forms of systemic cancer treatment but rarely integrated into clinical trial design or included within precision oncology initiatives. In this talk, we will investigate cancer treatment as a game-theoretic contest between the physician's therapy and the cancer cells' resistance strategies. This game has two critical asymmetries: (1) Only the physician can play rationally. Cancer cells, like all evolving organisms, can only adapt to current conditions; they can neither anticipate nor evolve adaptations for treatments that the physician has not yet applied. (2) It has a distinctive leader-follower (or "Stackelberg") dynamics; the "leader" oncologist plays first and the "follower" cancer cells then respond and adapt to therapy. Current treatment protocols for metastatic cancer typically exploit neither asymmetry. By repeatedly administering the same drug(s) until disease progression, the physician "plays" a fixed strategy even as the opposing cancer cells continuously evolve successful adaptive responses. By changing treatment only when the tumor progresses, treatment failure becomes nearly inevitable. Using game theory, we will see how physicians can exploit the advantages inherent in the asymmetries of the cancer treatment game, and likely improve outcomes, by adopting more dynamic treatment protocols that integrate eco-evolutionary dynamics and modulate therapy accordingly. Implementing this approach will require new metrics of tumor response that incorporate both ecological (i.e. size) and evolutionary (i.e. molecular mechanisms of resistance and relative size of resistant population) changes.
22 Nov 2018
Cancer Research UK Manchester Institute, United Kingdom