Resistance is not the end: lessons from pest management.

The "war on cancer" began over 40 years ago with the signing of the National Cancer Act of 1971. Currently, complete eradication has proven possible in early stage premetastatic disease with increasingly successful early detection and surgery protocols; however, late stage metastatic disease remains invariably fatal. One of the main causes of treatment failure in metastatic disease is the ability of cancer cells to evolve resistance to currently available therapies. Evolution of resistance to control measures is a universal problem. While it may seem that the mechanisms of resistance employed by cancer cells are impossible to control, we show that many of the resistance mechanisms are mirrored in agricultural pests. In this way, we argue that measures developed in the agricultural industry to slow or prevent pesticide resistance could be adopted in clinical cancer biology to do the same. The agriculture industry recognized the problem of pesticide resistance and responded by developing and enforcing guidelines on resistance management and prevention. These guidelines, known as integrated pest management (IPM), do not encourage eradication of pests but instead strive to maintain pests, even with the presence of resistant strains, at a level that does not cause economic damage to the crops. Integrated pest management inspired management of metastatic cancer could result in the slowing or curtailing of widespread resistance to treatment, reducing overall drug usage, and increasing the survival and quality of life of patients with cancer. Using IPM principles as a foundation and shifting the goal of treatment of metastatic disease to long-term management will require close monitoring of evolving tumor populations, judicious application of currently available therapies, and development of new criteria of success.