Details

Autor(en) / Beteiligte

• Palmer, Adam C.
• Sorger, Peter K.

Titel

Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy

Ist Teil von

• Cell, 2017-12, Vol.171 (7), p.1678-1691.e13

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Combination cancer therapies aim to improve the probability and magnitude of therapeutic responses and reduce the likelihood of acquired resistance in an individual patient. However, drugs are tested in clinical trials on genetically diverse patient populations. We show here that patient-to-patient variability and independent drug action are sufficient to explain the superiority of many FDA-approved drug combinations in the absence of drug synergy or additivity. This is also true for combinations tested in patient-derived tumor xenografts. In a combination exhibiting independent drug action, each patient benefits solely from the drug to which his or her tumor is most sensitive, with no added benefit from other drugs. Even when drug combinations exhibit additivity or synergy in pre-clinical models, patient-to-patient variability and low cross-resistance make independent action the dominant mechanism in clinical populations. This insight represents a different way to interpret trial data and a different way to design combination therapies. [Display omitted] •Anti-cancer drugs have variable efficacy within patient populations•Drug combinations give each patient more chances that one drug could be effective•Clinical efficacy of many combinations is accurately predicted without drug synergy•Optimizing drug independence represents a new way to design cancer treatments Patient-to-patient variability in response to single drugs is sufficient to explain the efficacy of a large number of combination cancer therapies without pharmacologically additive or synergistic effect in individual patients.