肿瘤处方的生殖系药物基因组学的现代进展

Reizine N M, O'donnell P H. Modern developments in germline pharmacogenomics for oncology prescribing[J]. CA Cancer J Clin, 2022.

The integration of genomic data into personalized treatment planning has revolutionized oncology care. Despite this, patients with cancer remain vulnerable to high rates of adverse drug events and medication inefficacy, affecting prognosis and quality of life. Pharmacogenomics is a field seeking to identify germline genetic variants that contribute to an individual's unique drug response. Although there is widespread integration of genomic information in oncology, somatic platforms, rather than germline biomarkers, have dominated the attention of cancer providers. Patients with cancer potentially stand to benefit from improved integration of both somatic and germline genomic information, especially because the latter may complement treatment planning by informing toxicity risk for drugs with treatment-limiting tolerabilities and narrow therapeutic indices. Although certain germline pharmacogenes, such as TPMT, UGT1A1, and DPYD, have been recognized for decades, recent attention has illuminated modern potential dosing implications for a whole new set of anticancer agents, including targeted therapies and antibody-drug conjugates, as well as the discovery of additional genetic variants and newly relevant pharmacogenes. Some of this information has risen to the level of directing clinical action, with US Food and Drug Administration label guidance and recommendations by international societies and governing bodies. This review is focused on key new pharmacogenomic evidence and oncology-specific dosing recommendations. Personalized oncology care through integrated pharmacogenomics represents a unique multidisciplinary collaboration between oncologists, laboratory science, bioinformatics, pharmacists, clinical pharmacologists, and genetic counselors, among others. The authors posit that expanded consideration of germline genetic information can further transform the safe and effective practice of oncology in 2022 and beyond.

将基因组数据整合到个性化治疗计划中已经彻底改变了肿瘤治疗。尽管如此，癌症患者仍然容易发生药物不良事件和药物无效，影响预后和生活质量。药物基因组学是一个领域，寻求确定生殖系遗传变异，有助于个人的独特药物反应。虽然在肿瘤学中有广泛的基因组信息整合，但体细胞平台，而不是生殖系生物标记物，已经主导了癌症提供者的关注。癌症患者可能受益于体细胞和生殖系基因组信息的改进整合，特别是因为后者可能通过告知具有治疗限制性耐受性和狭窄治疗指标的药物的毒性风险来补充治疗计划。尽管某些生殖系药物基因，如硫代嘌呤甲基转移酶（TPMT）、UGT1A1和DPYD，已经被认识了几十年，但最近的关注阐明了现代潜在的剂量影响，包括靶向治疗和抗体-药物偶联物，以及其他遗传变异和新相关药物基因的发现。其中一些信息已经上升到指导临床行动的水平，美国食品和药物管理局（FDA）的标签指导和国际社会和管理机构的建议。这篇综述集中在关键的新的药物基因组学证据和肿瘤特异性剂量建议。通过整合药物基因组学的个性化肿瘤护理代表了肿瘤学家、实验室科学、生物信息学、药剂师、临床药理学家和遗传顾问等之间独特的多学科合作。