Yau Tung On
John van Geest Cancer Research Centre, School of Science and Technology Nottingham Trent University Nottingham UK.
JGH Open. 2019 Feb 8;3(5):361-369. doi: 10.1002/jgh3.12153. eCollection 2019 Oct.
Until recently, a one-drug-fits-all model was applied to every patient diagnosed with the same condition. But not every condition is the same, and this has led to many cases of ineffective treatment. Pharmacogenetics is increasingly used to stratify patients for precision medicine treatments, for instance, the UGT1A1*28 polymorphism as a dosage indicator for the use of irinotecan as well as epidermal growth factor receptor (EGFR) immunohistochemistry and KRAS Proto-Oncogene () exon 2 mutation tests for determining the likelihood of treatment response to cetuximab or panitumumab treatment in metastatic colorectal cancer (CRC). The other molecular subtypes, such as exon 3/4, B-Raf Proto-Oncogene, , , and , were also reported as potential new pharmacogenetic targets for the current and the newly discovered anticancer drugs. In addition to next-generation sequencing (NGS), primary tumor cells for and drug screening, imaging biomarker 3'-Deoxy-3'-18F-fluorothymidine positron emission tomography, and circulating tumor DNA (ctDNA) detection methods are being developed and may represent the future direction of precision medicine. This review will discuss the current environment of precision medicine, including clinically approved targeted therapies, the latest potential therapeutic agents, and the ongoing pharmacogenetic trials for CRC patients.
直到最近,一种适用于所有被诊断患有相同疾病的患者的一刀切模式仍在应用。但并非所有疾病都是相同的,这导致了许多治疗无效的案例。药物遗传学越来越多地用于对患者进行分层以实施精准医学治疗,例如,UGT1A1*28多态性作为使用伊立替康的剂量指标,以及表皮生长因子受体(EGFR)免疫组化和KRAS原癌基因()外显子2突变检测,用于确定转移性结直肠癌(CRC)患者对西妥昔单抗或帕尼单抗治疗反应的可能性。其他分子亚型,如外显子3/4、B-Raf原癌基因、、和,也被报道为当前及新发现的抗癌药物潜在的新药物遗传学靶点。除了下一代测序(NGS)外,用于和药物筛选的原发性肿瘤细胞、成像生物标志物3'-脱氧-3'-18F-氟胸腺嘧啶正电子发射断层扫描以及循环肿瘤DNA(ctDNA)检测方法正在开发中,可能代表精准医学的未来方向。本综述将讨论精准医学的当前环境,包括临床批准的靶向治疗、最新的潜在治疗药物以及针对CRC患者正在进行的药物遗传学试验。