Modeling the cancer patient with genetically engineered mice: prediction of toxicity from molecule-targeted therapies.
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.
Roberts
Reade B
RB
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Arteaga
Carlos L
CL
Threadgill
David W
DW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001549:Benzamides; D018421:Cardiomyoplasty; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D016313:Genes, abl / Q000502:physiology; D005818:Genetic Engineering; D006801:Humans; D000068877:Imatinib Mesylate; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D012868:Skin Abnormalities / Q000139:chemically induced; D000068878:Trastuzumab; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001549:Benzamides; D007527:Isoenzymes; D008565:Membrane Proteins; D010879:Piperazines; D011743:Pyrimidines; D018125:Receptors, Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D000068877:Imatinib Mesylate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D000068878:Trastuzumab