Targeted agents: how to select the winners in preclinical and early clinical studies?

Eur J Cancer. 2012 Jan;48(2):170-8. doi: 10.1016/j.ejca.2011.09.024. Epub 2011 Nov 15.


There has been a significant shift within oncology drug development away from empiric screening of cytotoxic compounds to the era of genomics and molecularly targeted agents. The drug development process is evolving with greater emphasis on proof-of-mechanism studies in both preclinical and early clinical development. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Task Force, established as a forum for academic and pharmaceutical leaders to discuss methodological issues in targeted anticancer therapy development, met in March 2010 to review what were the minimal data required to make appropriate decisions about moving new targeted cancer agents from late preclinical development into phase I and from phase I into phase II trials. A number of specific questions were posed, and responses to each developed through survey, literature review and discussion at the face to face meeting of the MDICT Task Force. Consensus emerged around the necessity to demonstrate proof-of-mechanism and obtain information on key pharmacokinetic aspects of drug behaviour in late preclinical and early clinical trials. However, controversy remains on the extent of in vivo anti-tumour efficacy required to support clinical development of targeted agents. A systematic review of the data in this area would be informative. Further, while objective response in phase I trials may be a favourable signal about the potential activity of a new agent, debate exists around the weight that should be placed on the observation of stable disease or functional imaging changes in driving drug development decisions in the absence of observing either responses or convincing pharmacodynamic data in phase I. MDICT made a number of recommendations that may aid in future development of targeted agents.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Clinical Trials, Phase I as Topic / methods*
  • Clinical Trials, Phase II as Topic
  • Drug Design
  • Drug Evaluation, Preclinical / methods*
  • Health Planning Guidelines
  • Humans
  • Mice
  • Models, Animal
  • Neoplasms / drug therapy*
  • Therapies, Investigational / methods*


  • Antineoplastic Agents