14 December 2017, Pages 1678-1691. Combination cancer therapies aim to improve the probability and magnitude of therapeutic richard g hatton figure drawing pdf 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.
Check if you have access through your login credentials or your institution. This is a good article. Follow the link for more information. 17th century, and was said to have “brought London into Cheshire”.