Preclinical predictors of anticancer drug efficacy: critical assessment with emphasis on whether nanomolar potency should be required of candidate agents.

ABSTRACT: In the current paradigm of anticancer drug development, candidate compounds are evaluated by testing their in vitro potency against molecular targets relevant to carcinogenesis, their effect on cultured cancer cells, and their ability to inhibit cancer growth in animal models. We discuss the key assumptions inherent in these approaches. In recent years, great emphasis has been placed on selecting for development compounds with nanomolar in vitro potency, expecting that they will be efficacious and safer based on the assumption that they can be used at lower doses ("the nanomolar rule"). However, this rule ignores critical parameters affecting efficacy and toxicity such as physiochemical and absorption, distribution, metabolism and excretion properties, off-target effects, and multitargetin

SUBMITTER: Wong CC 

PROVIDER: S-EPMC3362883 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature