Ayoub Nehad, Lucas Courtney, Kaddoumi Amal
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana, USA.
Asian Pac J Cancer Prev. 2011;12(5):1127-40.
The impact of genomics and pharmacogenomics in the current arena of clinical oncology is well-established. In breast cancer, mutations in the BRCA1 and BRCA2 genes have been well-characterized to carry a high risk of the disease during a woman's lifespan. However, these high risk genes contribute to only a small proportion of the familial cases of breast cancer. Hence, further efforts aimed to study the contribution of genetic mutations in other genes, including the estrogen receptor gene, TP53, CYP19, and mismatch repair genes to further investigate the genetic component of breast cancer. Multiple pharmacogenomic studies have previously linked genetic variants in known pathways with treatment response in cancer patients. Currently, polymorphisms in drug metabolizing enzymes, efflux transporters, as well as, drug targets have shown correlations to variations in response and toxicity to commonly prescribed chemotherapeutic treatments of breast cancer. CYP2D6 variants have been correlated with tamoxifen response and interindividual variability seen. An emerging application of cancer genetics and pharmacogenetics involves the use of inherited or acquired genetic abnormalities to predict treatment toxicity or outcomes. Recently, methods that involve the scanning of entire genomes for common variants have begun to influence studies of cancer causation. Currently, treatment individualization for breast cancer can take place on the basis of few molecular targets including the estrogen receptor and the overexpression of the HER2 receptor. Overall, the current review summarizes the recent findings in the genetic and pharmacogenetic research of breast cancer and the advances made in personalization of treatment.
基因组学和药物基因组学在当前临床肿瘤学领域的影响已得到充分证实。在乳腺癌中，BRCA1和BRCA2基因的突变已被充分表征，表明女性在其一生中患该病的风险很高。然而，这些高风险基因仅占乳腺癌家族病例的一小部分。因此，需要进一步努力研究其他基因（包括雌激素受体基因、TP53、CYP19和错配修复基因）中的基因突变所起的作用，以进一步探究乳腺癌的遗传因素。此前，多项药物基因组学研究已将已知途径中的基因变异与癌症患者的治疗反应联系起来。目前，药物代谢酶、外排转运蛋白以及药物靶点的多态性已显示出与乳腺癌常用化疗治疗的反应和毒性差异相关。CYP2D6变异与他莫昔芬反应及个体间差异相关。癌症遗传学和药物遗传学的一个新兴应用涉及利用遗传或获得性基因异常来预测治疗毒性或结果。最近，扫描全基因组寻找常见变异的方法已开始影响癌症病因学研究。目前，乳腺癌的治疗个体化可基于少数分子靶点进行，包括雌激素受体和HER2受体的过表达。总体而言，本综述总结了乳腺癌遗传和药物遗传学研究的最新发现以及治疗个体化方面取得的进展。
