Cancer Pharmacogenomics: Early Promise, But Concerted Effort Needed

Abstract

The past decade has brought together substantial advances in human genome analysis and a maturation of understanding of tumor biology. While there is much progress still to be had, there are now several prominent examples in which tumor-associated somatic mutations have been used to identify cellular signaling pathways in tumors. This in turn has led to the development of targeted therapies, with somatic mutations serving as genomic predictors of tumor response and providing new leads for drug development. There is also a realization that germline DNA variants can help optimize cancer drug dosing and predict the susceptibility of patients to the adverse side effects of these drugs; knowledge that ultimately can be used to improve the benefit:risk ratio of cancer treatment for individual patients.

Association of Genetic Variations in XRCC1 and ERCC1 Genes with Sporadic Breast Cancer

“…Genetic variations, such as single nucleotide polymorphism (SNP) may exchange amino acids or modify DNA conformations, which is related to cancer risk or human disorders (11,12). Single nucleotide polymorphism molecular analysis could facilitate prognosis, diagnosis, and remedy of human disorders (13). With the crucial roles of DNA repairing machinery components in human genome integrity, it is possible to reveal significant appearances of nucleotide changes in the DNA repair genes and the risk of malignancies (14).…”

The Complexity of Mental Disorders

“…Besides, medical diagnosis, treatment and disease prevention have been innovated. For instance, EGFR mutation in lung cancer, KRAS mutation in colon and lung cancers, BRAF mutation in colon cancer have led to the identification of molecular markers to be used for diagnosis (McLeod, 2013).…”

Promise of Pharmacogenomics for Drug Discovery, Treatment and Prevention of Parkinson's Disease. A Perspective

“…The most extensively studied ADME genes are the cytochrome P450 (CYP450) family [13]. In clinical use are CYP2D6 for administering tamoxifen and codeine for treatment of cancer and pain management [14], as well as CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1 ) to avoid risk of hemorrhagic complications of the anticoagulant, warfarin [15]. Of closer relevance to PD is the use of tetrabenazine for treatment of Huntington's disease whose dosing is based, only in part, on CYP2D6 genotype [16] because the predictive value of this genotype is not high enough to accurately predict outcome by itself [17].…”