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Preclinical development of molecular-targeted agents for cancer

Alberto Ocana1, Atanasio Pandiella, Lillian L Siu

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

Nature Reviews. Clinical Oncology
|December 8, 2010
PubMed

Insights

Preclinical strategies for cancer drugs face high failure rates. New methods like genetically engineered mouse models and small-interfering RNAs improve the evaluation of molecular-targeted agents and drug combinations.

Area of Science:

  • Oncology
  • Pharmacology
  • Biotechnology

Background:

  • Molecular-targeted agents are crucial in cancer therapy.
  • High attrition rates in early clinical trials indicate preclinical development challenges.
  • Identifying effective agents to improve human cancer outcomes remains difficult.

Purpose of the Study:

  • To review current preclinical strategies for evaluating novel molecular-targeted agents in cancer.
  • To discuss the limitations of existing preclinical methods.
  • To propose strategies for enhancing preclinical drug development.

Main Methods:

  • Genetically engineered mouse models (GEMMs) for in vivo testing.
  • Small-interfering RNAs (siRNAs) for target validation and drug screening.
  • Evaluation of novel agents, including phosphatidylinositol 3-kinase (PI3K) and poly(ADP-ribose) polymerase (PARP) inhibitors.
  • Identification of promising targeted drug combinations.

Main Results:

  • GEMMs and siRNAs aid in developing novel targeted compounds.
  • These techniques facilitate the discovery of effective drug combinations.
  • Preclinical models are evolving to better predict clinical efficacy.

Conclusions:

  • Improved preclinical evaluation methods are essential for reducing drug attrition rates.
  • Advanced techniques like GEMMs and RNA interference offer promising avenues for cancer drug development.
  • Optimizing preclinical strategies can lead to more successful targeted cancer therapies.

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