Genes causing inherited cancer as beacons to identify the mechanisms of chemoresistance.

Mechanisms of resistance to cancer chemotherapy are poorly understood. Molecular pathways involving genes associated with inherited cancer syndromes could represent mechanisms of chemoresistance. Microarray techniques can identify simultaneous alterations in the mRNA expression of multiple genes, but identification of the exact mechanism responsible for a particular phenotype, including resistance to a specific drug, remains problematic. Genes in which mutations cause inherited cancers play vital roles in apoptosis, growth arrest and/or DNA repair, and are inactivated by somatic mutations, deletions or hypermethylation in most cancer tissues. Similarities between carcinogenic injury and cell damage created by chemotherapeutics suggests that somatic inactivation of such genes is crucially important to drug sensitivity.