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.

中文翻译：

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肿瘤处方种系药物基因组学的现代发展

将基因组数据整合到个性化治疗计划中彻底改变了肿瘤护理。尽管如此，癌症患者仍然容易出现药物不良事件和药物无效的高发生率，从而影响预后和生活质量。药物基因组学是一个寻求识别有助于个体独特药物反应的种系遗传变异的领域。尽管基因组信息在肿瘤学中广泛整合，但体细胞平台（而不是种系生物标志物）主导了癌症提供者的注意力。癌症患者可能会受益于体细胞和种系基因组信息整合的改善，尤其是因为后者可以通过告知具有治疗限制耐受性和狭窄治疗指数的药物的毒性风险来补充治疗计划。尽管某些种系药物基因，例如TPMT、UGT1A1和DPYD几十年来，人们已经认识到这一点，最近的关注阐明了现代抗癌药物潜在的剂量影响，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。根据美国食品和药物管理局的标签指导以及国际协会和管理机构的建议，其中一些信息已上升到指导临床行动的水平。本综述的重点是关键的新药物基因组证据和肿瘤学特定剂量建议。通过综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咨询师等之间独特的多学科合作。