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  • Review Article
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Preclinical development of molecular-targeted agents for cancer

Nature Reviews Clinical Oncology volume 8, pages 200–209 (2011)Cite this article

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Abstract

Molecular-targeted agents are increasingly used for the treatment of cancer. However, the attrition rate for drugs that enter early clinical trials is higher than for other branches of internal medicine, suggesting that preclinical development has not been successful in identifying agents that can modify the outcome of human cancer. New preclinical strategies including genetically engineered mouse models and small-interfering RNAs are being used to evaluate novel agents, and have aided in the development of compounds, such as inhibitors of phosphatidylinositol 3-kinase or poly(ADP-ribose) polymerase. In addition, these techniques have helped in the identification of promising combinations of targeted drugs. In this Review, we describe methods for the preclinical evaluation of novel agents, their limitations, and strategies for improvement.

Key Points

  • The attrition rate of potential new drugs in oncology is higher than for other therapeutic areas of medicine

  • Improvement in preclinical methods to evaluate potential anticancer agents could decrease the high attrition rate in oncology

  • Novel in vitro and in vivo models including cell lines with defined molecular properties, small-interfering RNA libraries and genetically-modified mice have helped in the development of novel agents

  • Drugs that are currently in development, such as poly(ADP-ribose) polymerase and phosphatidylinositol 3-kinase inhibitors, are examples of compounds that have been developed using the above models

  • Novel methods to provide better knowledge of mechanisms of action of potential anticancer agents could assist the development of new compounds

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Figure 1: Identification of potential anticancer drugs.
Figure 2: Preclinical models to evaluate anticancer drugs.
Figure 3: Methods to decrease attrition rate in drug development.

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Authors and Affiliations

  1. Medical Oncology Department and AECC Unit, Albacete University Hospital, Hermanos Falco 37, Albacete, 2006, Spain

    Alberto Ocana

  2. Institute of Molecular and Cellular Biology of Cancer (CIC), Campus Miguel de Unamuno, University of Salamanca (CSIC), Salamanca, 37007, Spain

    Atanasio Pandiella

  3. Division of Medical Oncology and Hematology, Princess Margaret Hospital and University of Toronto, 610 University Avenue, Toronto, M5G2M9, ON, Canada

    Lillian L. Siu & Ian F. Tannock

Authors
  1. Alberto Ocana
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  2. Atanasio Pandiella
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  3. Lillian L. Siu
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  4. Ian F. Tannock
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Contributions

A. Ocana and A. Pandiella researched data for the article. All authors provided a substantial contribution to the discussion of content. A. Ocana and I. F. Tannock wrote the manuscript and all authors contributed to the editing and review of the manuscript before submission.

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Correspondence to Ian F. Tannock.

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The authors declare no competing financial interests.

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Ocana, A., Pandiella, A., Siu, L. et al. Preclinical development of molecular-targeted agents for cancer. Nat Rev Clin Oncol 8, 200–209 (2011). https://doi.org/10.1038/nrclinonc.2010.194

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