Resistance Management for Cancer: Lessons from Farmers

One of the main reasons we have not been able to cure cancers is that drugs select for drug-resistant cancer cells. Pest managers face similar challenges with pesticides selecting for pesticide-resistant organisms. Lessons in pest management have led to four heuristics that can be translated to controlling cancers 1. limit use (of chemical controls or modes of action to the lowest practical levels) 2. diversify use (of modes of action largely through rotations of chemical controls) 3. partition chemistry (modes of action through space and time, which in effect is a refuge management strategy) and 4. include non-chemical methods. These principles are general to all cancers and cancer drugs, and thus should be employed to improve oncology. We review the parallel difficulties in controlling the evolution of drug resistance in pests and cancer cells, and describe the results of single- and multi-drug strategies in agriculture and oncology. We dissect the methods that pest managers use to prevent the evolution of pesticide resistance, showing how integrated pest management inspired the development of adaptive therapy in oncology to stabilize tumor size, and increase progression-free survival and quality of life of patients. Finally, we demonstrate these principles in a proposal for clinical trials in colorectal cancer.