Antileukemic drug effects in childhood acute lymphoblastic leukemia.
Cancer is the second most common cause of death in children between 1 and 15 years of age in industrialized countries. Although acute lymphoblastic leukemia (ALL) is still among the leading causes of death in childhood cancer, remarkable progress in treatment results has been made with this disease. With current antileukemic therapy, more than 80% of children with ALL can be cured. Antileukemic medications, however, are generally toxic and can cause significant adverse drug reactions. Moreover, some patients have leukemia cell clones that are resistant to conventional antileukemic treatment. Overall, a fifth of children with ALL will not be cured despite intensified therapy, including allogeneic stem cell transplantation. Pharmacogenomics aims to elucidate functionally relevant genomic determinants for drug disposition and response in order to establish valid pharmacogenomic models that can help to select medications and their dose based on a patient's genetic make-up. This review focuses on investigations that provide important basic insights into ALL pharmacogenomics and/or hold great promise in providing clinically valuable pharmacogenomic models that can help to improve childhood ALL treatment by facilitating appropriate dose individualization, optimal treatment selection and drug discovery.