Clinical pharmacogenetics in oncology: the paradigm of molecular targeted therapies.
Even though treatment of several types of solid tumors has improved in the past few years with the introduction of molecular targeted agents in the therapeutic armamentarium of the medical oncologist, response rates to these agents are generally modest. Increasing evidence is now revealing that genetic factors are affecting patients' response to these therapeutic agents as well as the frequency and intensity of toxic reactions. Importantly, pharmacogenetic analysis is now required for the administration of several molecular targeted agents in clinical practice. For the vast majority of these agents, however, data remain purely experimental. Herein, we provide an overview of the genetic changes (mutations and polymorphisms) that have been associated with response to treatment with anticancer molecular targeted agents. Special emphasis is given on molecules (monoclonal antibodies and tyrosine kinase inhibitors) that target critical mediators in the epidermal growth factor receptor (EGFR), the human epidermal growth factor receptor 2 (HER2/ERBB2/NEU) and the vascular endothelial growth factor receptor (VEGFR) pathways. The true clinical utility of these applications remains to be proven in future prospective, randomized clinical trials in large patient cohorts of all different ethnic backgrounds.
Mountzios
Giannis
G
Oncology Unit, 3rd Department of Medicine, Sotiria General Hospital, Athens Medical School, Building Z, 152 Mesogion Avenue, 115 27 Athens, Greece.
Sanoudou
Despina
D
Syrigos
Konstantinos N
KN
D004358:Drug Therapy / Q000379:methods; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy / Q000639:trends*; D009154:Mutation / Q000187:drug effects; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000187:drug effects; D057285:Precision Medicine / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D066246:ErbB Receptors; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D017978:Receptors, Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor