Walsh Robert, Goh Boon-Cher
Department of Haematology-Oncology, National University Cancer Institute Singapore, Singapore.
Department of Haematology-Oncology, National University Cancer Institute Singapore, Singapore; Cancer Science of Institute, National University of Singapore, Singapore; Department of Pharmacology, National University of Singapore, Singapore.
Chin Clin Oncol. 2019 Jun;8(3):24. doi: 10.21037/cco.2019.05.01.
Cancer drug development is proceeding at a rapid pace, with drug approvals in oncology outpacing the other disease indications. With high population growth and economic development of Asian countries, access to cancer drugs becomes a paramount necessity. Approval of these drugs is dependent on establishing their safety and efficacy in populations living in these countries. Ethnic and racial differences in drug pharmacokinetics, or drug receptor sensitivities may lead to differences in drug responses between populations. These differences may be due to intrinsic or extrinsic factors, and understanding of the magnitude of these differences and their etiologies is important. One key pharmacogenetic reason for ethnic variability of drug response arises from the different allelic frequencies of polymorphic drug-metabolising enzyme genes, resulting in altered drug disposition. Using race or ethnicity as a "biomarker" for pharmacotherapeutics is fraught with issues as they are difficult to define scientifically, and are considered more social constructs. Nonetheless, studying the genetics of ethno-geographical variability of drug response will allow genetic biomarkers to be uncovered, which would greatly facilitate precision medicine, and should justify broadening the involvement and accrual of patients from global diverse populations during the early phases of drug development for an oncology drug.
癌症药物研发正在迅速推进，肿瘤学领域的药物获批速度超过了其他疾病适应症。随着亚洲国家人口的高速增长和经济发展，获取癌症药物成为至关重要的需求。这些药物的获批取决于在这些国家的人群中确立其安全性和有效性。药物药代动力学或药物受体敏感性方面的种族差异可能导致不同人群之间的药物反应差异。这些差异可能是由于内在或外在因素引起的，了解这些差异的程度及其病因很重要。药物反应种族变异性的一个关键药物遗传学原因是多态性药物代谢酶基因的不同等位基因频率，导致药物处置改变。将种族或民族用作药物治疗的“生物标志物”充满问题，因为它们难以科学定义，且更多地被视为社会建构。尽管如此，研究药物反应的种族地理变异性的遗传学将有助于发现遗传生物标志物，这将极大地促进精准医学，并应证明在肿瘤药物研发的早期阶段扩大全球不同人群患者的参与和纳入是合理的。
