Pharmacogenomics in cancer treatment defining genetic bases for inter-individual differences in responses to chemotherapy.

PURPOSE OF REVIEW

Pharmacogenomics is evolving rapidly due to the expansion of genomics and proteomics, the emerging technologies, knowledge of the molecular basis of neoplasms and of drug pathways. This article will give an update on the genetic basis of variable therapeutic responses to anticancer agents in children.

RECENT FINDINGS

The majority of recent findings concern the pharmacogenetics of key components of acute lymphoblastic leukemia treatment, 6-mercaptopurine and methotrexate. This is not surprising given that leukemia is the most common cancer affecting children, accounting for 25-35% of childhood malignancies worldwide with acute lymphoblastic leukemia comprising 80% of leukemia cases. In certain patients treatment fails due to drug resistance, rendering acute lymphoblastic leukemia the leading cause of cancer-related death in children. Most of the studies use a candidate gene approach adding a new body of evidence to existing knowledge. Recent findings relating to other childhood tumors and the potential to optimize treatment of these malignancies are briefly discussed.

SUMMARY

Interindividual differences in drug responses are an important cause of resistance to treatment and adverse drug reactions. Pharmacogenetics tends to identify the genetic basis of these suboptimal responses allowing traditional treatment to be complemented by genotype-based drug dose adjustment.