Al-Mahayri Zeina N, Patrinos George P, Ali Bassam R
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece.
Front Pharmacol. 2020 Apr 15;11:445. doi: 10.3389/fphar.2020.00445. eCollection 2020.
Breast cancer (BC) is one of the most prevalent types of cancer worldwide with high morbidity and mortality rates. Treatment modalities include systemic therapy, in which chemotherapy is a major component in many cases. Several chemotherapeutic agents are used in combinations or as single agents with many adverse events occurring in variable frequencies. These events can be a significant barrier in completing the treatment regimens. Germline genomic variants are thought of as potential determinants in chemotherapy response and the development of side effects. Some pharmacogenomic studies were designed to explore germline variants that can be used as biomarkers for predicting developing toxicity or adverse events during chemotherapy in BC. In this review, we reassess and summarize the major findings of pharmacogenomic studies of chemotherapy toxicity during BC management. In addition, deficiencies hampering utilizing these findings and the potential targets of future research are emphasized. Main insufficiencies in toxicity pharmacogenomics studies originate from study design, sample limitations, heterogeneity of selected genes, variants, and toxicity definitions. With the advent of high throughput genotyping techniques, researchers are expected to explore the identified as well as the potential genetic biomarkers of toxicity and efficacy to improve BC management. However, to achieve this, the limitations of previous work should be evaluated and avoided to reach more conclusive and translatable evidence for personalizing BC chemotherapy.
乳腺癌(BC)是全球最常见的癌症类型之一,发病率和死亡率都很高。治疗方式包括全身治疗,在许多情况下,化疗是主要组成部分。几种化疗药物可联合使用或单独使用,会出现多种频率不一的不良事件。这些事件可能是完成治疗方案的重大障碍。种系基因组变异被认为是化疗反应和副作用发生的潜在决定因素。一些药物基因组学研究旨在探索可作为生物标志物的种系变异,用于预测BC化疗期间毒性或不良事件的发生。在本综述中,我们重新评估并总结了BC治疗期间化疗毒性的药物基因组学研究的主要发现。此外,还强调了妨碍利用这些发现的不足之处以及未来研究的潜在目标。毒性药物基因组学研究的主要不足源于研究设计、样本局限性、所选基因、变异体的异质性以及毒性定义。随着高通量基因分型技术的出现,有望探索出已确定的以及潜在的毒性和疗效基因生物标志物,以改善BC的治疗。然而,要实现这一点,应评估并避免先前工作的局限性,从而获得更具决定性和可转化的证据,实现BC化疗的个性化。