Table 1.

Level of previous human experience for a selection of candidates being evaluated in NCI, DCP-sponsored cancer prevention studies

Level of previous human experiencePossible avenue of discoveryExamplesGoals of initial clinical development in cancer prevention setting
NoneNCE or analogue discovered during rational drug design or high-throughput screeningSR13668 (synthetic AKT pathway inhibitor); 9-cis- UAB30 (retinoid analogue)Establish first-in-human safety and bioavailability; verify applicability of preclinical safety, pharmacokinetics, and pharmacodynamic data; choose variant with best profile for continued development
Little or SomePurified compound (isolated or synthetic) found in food; botanical extracts; new formulation of existing compound designed to have altered bioavailability; existing food or dietary supplement being evaluated as a drug; continued development of chemopreventive agent of interestPolyphenon E (green tea extract); indole-3- carbinol (found in cruciferous vegetables); G-2535 (genistein-rich isoflavone mixture)Investigate dose effect and dose response; establish lowest effective dose; establish human safety and ADME at lowest effective dose; generate early evidence of efficacy
SubstantialRepurposing of over-the- counter or prescription drug for new indication; food componentPioglitazone; celecoxib; aspirin; ursodiolEstablish lowest effective dose; establish safety and ADME with long-term administration; generate early evidence of efficacy

Abbreviations: ADME, absorption, distribution, metabolism and excretion; NCE, new chemical entity.