Genomic strategies to improve outcome and individualize therapy in cancer: the paradigm of childhood acute lymphoblastic leukemia.
Childhood acute lymphoblastic leukemia (ALL) is the classic example for a drug-responsive malignancy, and contemporary risk-directed therapies cure more than 80% of children with ALL in industrialized countries. Antileukemic medications, however, can cause significant adverse drug reactions. Moreover, some children have leukemia cell clones which are resistant to current antileukemic treatment. As ALL is still among the leading causes of death from disease in children aged one to 15 years, further improvement of childhood ALL therapy is urgently needed. The aim of pharmacogenomics is to elucidate functionally relevant genomic determinants for drug disposition and response in order to optimize drug therapy based on a patient's genomic profile. Pharmacogenomics has evolved from the study of single candidate genes to large-scale genome-wide strategies. Results from recent pharmacogenomic investigations in children with ALL hold promise to improve ALL therapy in the near future; and can serve as a model to improve drug therapy in other malignancies as well.
St. Anna Children's Hospital, Vienna, Austria. leo.kager@stanna.at
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D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D010597:Pharmacogenetics / Q000379:methods*; D057285:Precision Medicine / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy*
D000970:Antineoplastic Agents; D008727:Methotrexate