Resistance is not the end: lessons from pest management

Abstract

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.

Stochastic competitive release and adaptive chemotherapy

“…The emergence of chemo-resistance in a tumor is the leading cause of progression to metastatic disease, and one of the biggest challenges facing oncologists in treating cancer patients [1][2][3][4][5]. The idea of managing resistance to chemotoxins in a tumor via adaptive scheduling [6,7] emerged relatively recently from lessons learned in the field of evolutionary ecology where the goal of pest eradication has been replaced with the idea of pest management using multi-pesticide adaptive dosing schedules that are actively monitored, managed, and regulated [8,9] so as to sustain ongoing competition among a multitude of insect species to avoid selecting for a resistant sub-type [10]. The idea that pesticides impose selection pressure on the sensitive pest population , thereby selecting for a resistant strain is by now well established [8].…”

Marine Natural Products: The Important Resource of Biological Insecticide

“…However, chemically synthesized pesticides are often resistant to pests while exerting effects due to their single composition [5] . Resistance leads to a reduction in pest prevention effect and increases the use of dosages, this vicious circle not only causes pesticide failure, but also results in serious environmental pollution [6–8] . Natural products are secondary metabolites naturally presented in animals, plants and microorganisms in nature, it is considered an important resource for a variety of chemical applications because of rich structure, excellent activity and environmental‐friendly features [9,10] …”

Special Collection on Ecological and Evolutionary Approaches to Cancer Control: Cancer Finds a Conceptual Home

“…Jessica Cunningham and Chris Whelan argue that the field of cancer biology, together with the pharmaceutical industry that develops new drugs, can benefit from studying the response of the agricultural industry to essentially the same problem: inevitably, it seems, pest organisms evolve resistance to pesticides. 25 Despite the obvious differences between cancer cells within the tumor ecosystem and pests within agricultural ecosystems, similar resistance mechanisms are found in both. integrated pest management (IPM), an important response to the evolution of resistance in pests, is the combined use of multiple, complementary methods of pest management.…”