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文献精选 > 近年高分"CRISPR基因编辑"研究（IF≥30，近5年）

Modern developments in germline pharmacogenomics for oncology prescribing. ​

文献信息 ​

DOI10.3322/caac.21722
PMID35302652
期刊CA: a cancer journal for clinicians
影响因子232.4
JCR 分区Q1
发表年份2022
被引次数5
关键词癌症，化疗，肿瘤学，个性化医学，药物基因组学
文献类型Journal Article, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
ISSN0007-9235
页码315-332
期号72(4)
作者Natalie M Reizine, Peter H O'Donnell

一句话小结 ​

本研究探讨了药物基因组学在个性化肿瘤学护理中的重要性，指出尽管基因组数据已被广泛应用，癌症治疗仍需加强对种系生物标志物的关注，以减少不良药物事件和提高治疗效果。通过整合体细胞和种系基因组信息，研究为改善癌症患者的预后和生活质量提供了新的视角，强调了多学科合作在实现个性化治疗中的关键作用。

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癌症 · 化疗 · 肿瘤学 · 个性化医学 · 药物基因组学

摘要 ​

将基因组数据纳入个性化治疗计划已经彻底改变了肿瘤学护理。尽管如此，癌症患者仍然面临高比例的不良药物事件和药物无效性，这影响了他们的预后和生活质量。药物基因组学是一个旨在识别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的广泛应用，癌症治疗提供者的关注主要集中在体细胞平台，而非种系生物标志物。癌症患者可能会从更好地整合体细胞和种系基因组信息中受益，特别是后者可以通过提供药物毒性风险的信息来补充治疗计划，尤其是对于那些具有治疗限制耐受性和窄治疗指数的药物。虽然某些种系药物基因（如TPMT、UGT1A1和DPYD）已被认识数十年，但近期的关注揭示了一整套新型抗癌药物（包括靶向疗法和抗体药物偶联物）的现代剂量潜在影响，以及额外遗传变异和新相关药物基因的发现。这些信息中的一些已经达到指导临床行动的水平，包括美国食品药品监督管理局的标签指导和国际学会及管理机构的建议。这篇综述重点讨论了关键的新药物基因组学证据和肿瘤学特定的剂量建议。通过整合药物基因组学实现的个性化肿瘤学护理，代表了肿瘤学家、实验室科学家、生物信息学家、药剂师、临床药理学家和遗传咨询师等多个学科之间独特的多学科合作。作者认为，扩大对种系遗传信息的考虑可以进一步转变肿瘤学的安全有效实践，尤其是在2022年及以后。

英文摘要 ​

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.

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主要研究问题 ​

  1. 在肿瘤药物治疗中，如何评估和整合体细胞和胚系基因组信息的有效性？
  2. 近年来，哪些新的胚系药物基因组学研究成果对癌症治疗产生了显著影响？
  3. 在个性化肿瘤治疗中，药物基因组学如何帮助降低不良药物事件的发生率？
  4. 针对特定抗癌药物，如何确定合适的药物剂量与患者的胚系遗传变异之间的关系？
  5. 不同国家和地区在肿瘤药物基因组学应用方面的政策和实践有何异同？

核心洞察 ​

研究背景和目的 ​

癌症患者在个体化治疗中面临高风险的不良药物事件和药物疗效不足，这对预后和生活质量产生了负面影响。药物基因组学旨在识别个体独特药物反应的种系遗传变异。尽管肿瘤学中已广泛整合基因组信息，但癌症治疗中更多关注的是体细胞生物标志物，而忽视了种系生物标志物。本文旨在探讨如何通过更好地整合种系和体细胞基因组信息来改善癌症患者的治疗计划。

主要方法/材料/实验设计 ​

本研究采用文献综述的方法，综合分析了药物基因组学在肿瘤学中的应用，重点关注种系药物基因的现代剂量影响及其对新型抗癌药物的影响。以下是技术路线的流程图：

Mermaid diagram

关键结果和发现 ​

  1. 种系药物基因（如TPMT、UGT1A1、DPYD）在药物反应中的重要性被重新审视，特别是对于新型靶向治疗和抗体药物偶联物。
  2. 一些遗传变异已上升到指导临床行动的水平，包括美国食品药品监督管理局（FDA）的标签指导和国际学会的建议。
  3. 整合种系和体细胞基因组信息有助于识别药物的毒性风险，尤其是对于治疗限制性耐受性和窄治疗指数的药物。

主要结论/意义/创新性 ​

个体化肿瘤学护理通过整合药物基因组学展现了多学科协作的潜力。扩大对种系遗传信息的考虑可以进一步转变肿瘤学的安全有效实践，尤其是在2022年及以后。这种整合不仅有助于优化治疗方案，还可能提高患者的生活质量。

研究局限性和未来方向 ​

  1. 局限性：本研究主要基于文献综述，缺乏大规模临床试验的数据支持。
  2. 未来方向：
    • 需要更多的前瞻性研究来验证种系药物基因组学的实际应用效果。
    • 应推动多学科团队合作，以促进药物基因组学在临床实践中的广泛应用。
    • 未来研究应关注新发现的药物基因和遗传变异，以便更好地指导个体化治疗。

通过这些努力，药物基因组学有望在癌症治疗中发挥更大的作用，从而改善患者的预后和生活质量。

参考文献 ​

  1. Mechanisms of Chemotherapy-Induced Peripheral Neuropathy. - Renata Zajączkowska;Magdalena Kocot-Kępska;Wojciech Leppert;Anna Wrzosek;Joanna Mika;Jerzy Wordliczek - International journal of molecular sciences (2019)
  2. HLA-B*57:01 screening and hypersensitivity reaction to abacavir between 1999 and 2016 in the OPERA® observational database: a cohort study. - Karam Mounzer;Ricky Hsu;Jennifer S Fusco;Laurence Brunet;Cassidy E Henegar;Vani Vannappagari;Chris M Stainsby;Mark S Shaefer;Leigh Ragone;Gregory P Fusco - AIDS research and therapy (2019)
  3. Haplotypes of variants in the UDP-glucuronosyltransferase1A9 and 1A1 genes. - Federico Innocenti;Wanqing Liu;Peixian Chen;Apurva A Desai;Soma Das;Mark J Ratain - Pharmacogenetics and genomics (2005)
  4. Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry. - Takaya Moriyama;Yung-Li Yang;Rina Nishii;Hany Ariffin;Chengcheng Liu;Ting-Nien Lin;Wenjian Yang;Dong-Tsamn Lin;Chih-Hsiang Yu;Shirley Kham;Ching-Hon Pui;William E Evans;Sima Jeha;Mary V Relling;Allen Eng-Juh Yeoh;Jun J Yang - Blood (2017)
  5. Race and Pharmacogenomics-Personalized Medicine or Misguided Practice? - Christopher W Goodman;Allan S Brett - JAMA (2021)
  6. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. - Tai-Ming Ko;Chang-Youh Tsai;Shih-Yang Chen;Kuo-Shu Chen;Kuang-Hui Yu;Chih-Sheng Chu;Chung-Ming Huang;Chrong-Reen Wang;Chia-Tse Weng;Chia-Li Yu;Song-Chou Hsieh;Jer-Chia Tsai;Wen-Ter Lai;Wen-Chan Tsai;Guang-Dar Yin;Tsan-Teng Ou;Kai-Hung Cheng;Jeng-Hsien Yen;Teh-Ling Liou;Tsung-Hsien Lin;Der-Yuan Chen;Pi-Jung Hsiao;Meng-Yu Weng;Yi-Ming Chen;Chen-Hung Chen;Ming-Fei Liu;Hsueh-Wei Yen;Jia-Jung Lee;Mei-Chuan Kuo;Chen-Ching Wu;Shih-Yuan Hung;Shue-Fen Luo;Ya-Hui Yang;Hui-Ping Chuang;Yi-Chun Chou;Hung-Ting Liao;Chia-Wen Wang;Chun-Lin Huang;Chia-Shuo Chang;Ming-Ta Michael Lee;Pei Chen;Chih-Shung Wong;Chien-Hsiun Chen;Jer-Yuarn Wu;Yuan-Tsong Chen;Chen-Yang Shen; - BMJ (Clinical research ed.) (2015)
  7. Identification of Incidental Germline Mutations in Patients With Advanced Solid Tumors Who Underwent Cell-Free Circulating Tumor DNA Sequencing. - Thomas P Slavin;Kimberly C Banks;Darya Chudova;Geoffrey R Oxnard;Justin I Odegaard;Rebecca J Nagy;Kar Wing Kevin Tsang;Susan L Neuhausen;Stacy W Gray;Massimo Cristofanilli;Angel A Rodriguez;Aditya Bardia;Brian Leyland-Jones;Mike F Janicek;Michael Lilly;Guru Sonpavde;Christine E Lee;Richard B Lanman;Funda Meric-Bernstam;Razelle Kurzrock;Jeffrey N Weitzel - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2018)
  8. Effects of UGT1A1 genotype on the pharmacokinetics, pharmacodynamics, and toxicities of belinostat administered by 48-hour continuous infusion in patients with cancer. - Andrew K L Goey;Tristan M Sissung;Cody J Peer;Jane B Trepel;Min-Jung Lee;Yusuke Tomita;Sheryl Ehrlich;Christine Bryla;Sanjeeve Balasubramaniam;Richard Piekarz;Seth M Steinberg;Susan E Bates;William D Figg - Journal of clinical pharmacology (2016)
  9. Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. - C-F Xu;B H Reck;Z Xue;L Huang;K L Baker;M Chen;E P Chen;H E Ellens;V E Mooser;L R Cardon;C F Spraggs;L Pandite - British journal of cancer (2010)
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引用本文的文献 ​

  1. Genetic Influences in Cancer-Associated Myositis. - Karina Patasova;Ingrid E Lundberg;Marie Holmqvist - Arthritis & rheumatology (Hoboken, N.J.) (2023)
  2. Advances in Pharmacy Practice: A Look towards the Future. - Jeffrey Atkinson - Pharmacy (Basel, Switzerland) (2022)
  3. Characterization of Oncology Clinical Trials Using Germline Genetic Data. - Ashwin V Kammula;Alejandro A Schäffer;Padma Sheila Rajagopal - JAMA network open (2022)
  4. Overcoming Barriers to Discovery and Implementation of Equitable Pharmacogenomic Testing in Oncology. - Sharon P Shriver;Devon Adams;Brittany Avin McKelvey;Jeannine S McCune;Dale Miles;Victoria M Pratt;Kristine Ashcraft;Howard L McLeod;Hannah Williams;Mark E Fleury - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2024)
  5. Moving toward precision medicine to predict drug sensitivity in patients with metastatic breast cancer. - M Bottosso;F Mosele;S Michiels;P-H Cournède;S Dogan;C Labaki;F André - ESMO open (2024)

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