Tumor-specific genetic lesions and their influence on therapy in pediatric acute lymphoblastic leukemia.

Pharmacogenomics has traditionally focused on the identification of inherited genetic differences that influence a patient's response to a specific therapeutic agent. These differences can range from inherited variability in the genes that affect drug absorption, distribution, intracellular transport, metabolism, and elimination, to variability in the genes that encode either the target of the drug or components of the pathway affected by the drug. The main goal of pharmacogenomics is to improve our understanding of how these variations, either individually or collectively, influence the therapeutic response. The genetic differences inherent within cancer cells constitute the other major variable in a patient's ultimate response to therapy. In this review, we provide an overview of high-throughput genomic methods that can be used to identify genetic lesions within cancer cells. These efforts will ultimately allow the identification of the full complement of genetic lesions that underlie the establishment and maintenance of the leukemic clone. The identification of these lesions should provide the bases for defining the molecular "Achilles heels" against which new targeted therapies can be developed.