Grants - Florida - Designated Grants - 2016

Robert Gatenby, M.D.

The Robert Shields Memorial Grant for Esophageal Cancer was funded by two fundraisers organized by Frank Cannata:  Rolling Thunder’s 2015 “Ride for Freedom,” and The Cannata Report Awards and Charities Dinner

Unlike treatment of other common diseases, cancer therapy is constantly limited by rapid evolution of resistance in the treated (cancer) cells. Unfortunately, the amazing capacity of tumor cells to evolve resistance strategies limits virtually every treatment so that metastatic cancers generally remain fatal.

We propose that, while the ability to evolve confers a great advantage on cancer cells, it also imposes a subtle opportunity for treatment. This is because evolving populations can only adapt to current conditions – they can never anticipate future environments. Importantly we can.  In this project we employ a sequence of treatments. The first therapy both actively kills cancer cells and guides the evolution of cancer cells so that development of resistance, although inevitable, uses a cellular strategy that we can attack with the second line therapy. We term this “double bind” cancer treatment strategy. An excellent illustration of this approach is pest management through “predator facilitation.” For example, in the event of a rodent infestation, a farmer may introduce an owl. However, rodents typically adapt to the owl predation by shifting their activity to the safety of shrubs. While this would seem to be discouraging result (similar to evolution of resistance to therapy in cancer), the “resistance” strategy can, in fact, be exploited by the farmer by introducing snakes. This is a double bind because the owls facilitate the hunting success of snakes and vice-versa. In this project we construct a similar evolutionary dynamics for treating esophageal cancer using a combination of target therapy and immunotherapy.