Resistance Management for Cancer: Lessons from Farmers

Abstract

One of the main reasons we have not been able to cure cancers is that treatments select for drug-resistant cells. Pest managers face similar challenges with pesticides selecting for pesticide-resistant insects, resulting in similar mechanisms of resistance. Pest managers have developed 10 principles that could be translated to controlling cancers: (i) prevent onset, (ii) monitor continuously, (iii) identify thresholds below which there will be no intervention, (iv) change interventions in response to burden, (v) preferentially select nonchemical control methods, (vi) use target-specific drugs, (vii) use the lowest effective dose, (viii) reduce cross-resistance, (ix) evaluate success based on long-term management, and (x) forecast growth and response. These principles are general to all cancers and cancer drugs and so could be employed broadly to improve oncology. Here, we review the parallel difficulties in controlling drug resistance in pests and cancer cells. We show how the principles of resistance management in pests might be applied to cancer. Integrated pest management inspired the development of adaptive therapy in oncology to increase progression-free survival and quality of life in patients with cancers where cures are unlikely. These pest management principles have the potential to inform clinical trial design.

Figure 1.

Lessons from IPM to oncology. A, These are the best practices in pest management and how they might be applied in cancer treatment. B, Comparison of standard therapy with two models of adaptive therapy. In standard therapy (A), the MTD of a drug is used. In dose modulation adaptive therapy (B), the dose of the drugs is adjusted based on the tumor’s response. In drug holiday (C) treatment skipping, the MTD of the drug is used until the tumor shrinks and then the treatment is skipped. CAR, chimeric antigen receptor.

Figure 2.

Schematic of a MoA schedule. A, In pest management, pest managers avoid sequential use of the same MoA and avoid using a MoA more than twice within the same growing season. To avoid cancer cells acquiring therapeutic resistance, repeated applications of a MoA should be separated as much as possible. B, Proposed scheduling of drugs that applies each drug once per 4-week cycle and uses different MoAs. The third week of each cycle uses an antiangiogenic drug to avoid restricting the vasculature before trying to deliver the other drugs. Week 4 of each cycle is a drug holiday break to allow the patient to recover.