Investigating tumor microenvironment: ecology and evolutionary dynamics for cancer.

The evolution of resistance is a fundamental problem in disease management. Cancers in different patients appear to follow the same eco-evolutionary path that independently manifests in affected patients. This convergent outcome, that always includes therapeutic resistance, demands an explanation beyond the slow and steady accrual of stochastic mutations. Microenvironmental stress contribute to and drives cancer cell evolution. To further understand and evaluate cellular responses to stress, we tracked single-cell dynamics through time in response to microenvironmental and cytotoxic therapy at the molecular and cellular level. We have identified exit from the mitotic cycle and entry into the endocycle as a previously undefined potential mechanism of cell evolvability, improvement in fitness, and survival. Understanding that cancer cells can swiftly evolve responses to novel and varied stressors create opportunities for adaptive therapy, double-bind therapies, and extinction therapies; all involving strategic decision making that steers and anticipates the convergent coevolutionary responses of the cancers.