University of California San Francisco School of Pharmacy, Palo Alto, Menlo Park, CA 94025, USA.
J Oncol Pharm Pract. 2023 Jul;29(5):1187-1195. doi: 10.1177/10781552231153814. Epub 2023 Feb 3.
The intent of this review is to present basic genetic concepts key to understanding oncogenesis and the role receptor tyrosine kinase (RTK) inhibition plays in the targeted treatment of many cancer types. Oncogenic signaling by RTKs can result from genetic events such as point mutations, chromosomal rearrangements, structural variation, and gene amplification in the cancer genome. The cancer pharmacogenes discussed encode RTKs that exemplify the link between gene variation, the oncogenic process, and the basis of targeted approaches to treatment. Biochemical pathways often involved in oncogenesis and affected by RTK variation are reviewed. Molecular diagnostic testing for the presence of specific gene variants, alterations, and amplifications direct therapy to indicated tyrosine kinase inhibitors and monoclonal antibody drugs. As pharmacists are integral to the selection, preparation, and monitoring of chemotherapy, it is important that they understand the genetic basis for targeted therapies as well as the underlying disease process.
本文旨在介绍理解肿瘤发生和受体酪氨酸激酶 (RTK) 抑制在多种癌症类型的靶向治疗中所起作用的关键基础遗传学概念。RTK 的致癌信号可以源于遗传事件，如点突变、染色体重排、结构变异和癌症基因组中的基因扩增。所讨论的癌症药物相关基因编码 RTK，它们体现了基因变异、致癌过程和针对治疗方法的基础之间的联系。还回顾了经常涉及肿瘤发生并受 RTK 变异影响的生化途径。针对特定基因突变、改变和扩增的分子诊断检测指导针对特定酪氨酸激酶抑制剂和单克隆抗体药物的治疗。由于药剂师是化疗选择、准备和监测的重要组成部分，因此了解靶向治疗的遗传基础以及潜在疾病过程非常重要。
