Modeling the cancer patient with genetically engineered mice: prediction of toxicity from molecule-targeted therapies

Cancer Cell. 2004 Feb;5(2):115-20. doi: 10.1016/s1535-6108(04)00032-7.

Abstract

Current trends foretell the use of cancer treatments customized to each patient. Genetic and molecular profiling of tumors and an increasing number of molecule-targeted therapies contribute to making this a reality. However, as targets of anticancer therapies become specific proteins or pathways, unanticipated side effects may emerge. In addition, the chronic use of these treatments may contribute to the development of degenerative toxicity not predicted by short-term clinical trials. Here we review and propose how genetically engineered mouse models can serve as valuable tools to predict targeted therapy toxicity, as well as to identify allelic variants that predispose individuals to side effects.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Benzamides
  • Cardiomyoplasty
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / physiopathology
  • Cyclooxygenase 2
  • Disease Models, Animal
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism*
  • Gastrointestinal Diseases / chemically induced
  • Genes, abl / physiology
  • Genetic Engineering
  • Humans
  • Imatinib Mesylate
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Membrane Proteins
  • Mice
  • Mice, Transgenic / genetics
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Piperazines / adverse effects
  • Piperazines / pharmacology
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Receptors, Transforming Growth Factor beta / metabolism
  • Skin Abnormalities / chemically induced
  • Trastuzumab
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Benzamides
  • Isoenzymes
  • Membrane Proteins
  • Piperazines
  • Pyrimidines
  • Receptors, Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Imatinib Mesylate
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • ErbB Receptors
  • Receptors, Platelet-Derived Growth Factor
  • Trastuzumab