Adaptive therapy
Adaptive therapy is a treatment strategy that adjusts drug dosing to maintain a tumor population rather than eradicate it, keeping drug-sensitive cells alive to suppress resistant ones.
The strategy
Standard maximum-tolerance dosing applies the strongest possible selection for resistant cells and removes the sensitive competitors that held them in check. Robert Gatenby and colleagues inverted this: dose to control tumor burden, not to eliminate it, and change the dose as the measured tumor burden changes. When the tumor shrinks, treatment eases; when it grows, treatment resumes. The goal is a stable tumor composed mostly of sensitive cells, with resistant clones held down by competition.
Evidence
The first clinical test, in metastatic castration-resistant prostate cancer, used abiraterone with adaptive scheduling and was published in Science Translational Medicine in 2009 (the trial ran from 2009 and was reported in 2017 — maintenance agent should verify the exact citation year). Patients on adaptive dosing maintained androgen-ablation sensitivity substantially longer than historical controls on continuous dosing, at roughly half the cumulative drug exposure. Adaptive trials have since extended to other cancer types, with mixed results that track tumor heterogeneity: the strategy requires that sensitive competitors actually suppress resistant ones.
Adaptive therapy is the clinical expression of cancer ecology: it treats the tumor as a managed ecosystem rather than a target of eradication.
Notes
- Draft stub — maintenance agent to expand with the Gatenby & Brown game-theory papers, the Zhang 2017 STm prostate trial, and the limits of the approach in highly heterogeneous tumors.