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Modern developments in germline pharmacogenomics for oncology prescribing.
Literature Information
| DOI | 10.3322/caac.21722 |
|---|---|
| PMID | 35302652 |
| Journal | CA: a cancer journal for clinicians |
| Impact Factor | 232.4 |
| JCR Quartile | Q1 |
| Publication Year | 2022 |
| Times Cited | 5 |
| Keywords | cancer, chemotherapy, oncology, personalized medicine, pharmacogenomics |
| Literature Type | Journal Article, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't |
| ISSN | 0007-9235 |
| Pages | 315-332 |
| Issue | 72(4) |
| Authors | Natalie M Reizine, Peter H O'Donnell |
TL;DR
This review highlights the critical role of pharmacogenomics in enhancing personalized oncology care by integrating germline genetic variants with somatic genomic information, which can significantly inform drug dosing and toxicity risk for cancer treatments. The findings suggest that incorporating a broader range of germline biomarkers into clinical practice can improve patient outcomes by mitigating adverse drug events and optimizing therapeutic efficacy.
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cancer · chemotherapy · oncology · personalized medicine · pharmacogenomics
Abstract
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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Primary Questions Addressed
- How do recent advancements in germline pharmacogenomics compare to traditional somatic genomic approaches in oncology?
- What are the specific challenges faced by oncologists in integrating germline pharmacogenomic data into clinical practice?
- How can the identification of new pharmacogenes impact the development of future anticancer therapies?
- In what ways can multidisciplinary collaboration enhance the application of germline pharmacogenomics in personalized oncology care?
- What role do regulatory bodies play in shaping the guidelines for germline pharmacogenomic testing in oncology?
Key Findings
Research Background and Objectives
The integration of genomic data into personalized treatment planning has significantly transformed oncology care. However, patients with cancer still experience high rates of adverse drug events and ineffective medication, impacting their prognosis and quality of life. The objective of this review is to explore the role of pharmacogenomics in identifying germline genetic variants that influence individual drug responses, highlighting the need for a more integrated approach that combines both somatic and germline genomic information in oncology.
Main Methods/Materials/Experimental Design
The review synthesizes recent advancements in pharmacogenomics, focusing on germline biomarkers that can inform treatment decisions. The authors discuss the implications of these genetic variants on dosing recommendations for various anticancer therapies. The methodology includes a comprehensive analysis of existing literature, clinical guidelines, and pharmacogenomic evidence related to oncology.
Key Results and Findings
- Germline Pharmacogenes: Specific genes such as TPMT, UGT1A1, and DPYD have long been recognized for their role in drug metabolism, but new pharmacogenes are emerging with implications for modern therapies.
- Dosing Implications: Recent studies indicate that understanding germline variants can significantly influence dosing strategies for targeted therapies and antibody-drug conjugates.
- Clinical Guidelines: The integration of pharmacogenomic data has led to new recommendations from the US FDA and international societies, directing clinical practice towards safer and more effective treatments.
Main Conclusions/Significance/Innovation
The review underscores the importance of integrating both somatic and germline genomic information in oncology to enhance personalized treatment approaches. The authors argue that a multidisciplinary collaboration among oncologists, pharmacists, genetic counselors, and bioinformaticians is essential for implementing pharmacogenomics in clinical practice. This approach promises to improve patient safety and treatment efficacy, marking a significant advancement in personalized oncology care.
Research Limitations and Future Directions
- Limitations: The review acknowledges that while germline pharmacogenomics has potential, the current focus on somatic mutations may overshadow the benefits of germline variants. Additionally, there may be gaps in the availability of genetic testing and education among healthcare providers.
- Future Directions: The authors advocate for further research into the clinical utility of germline pharmacogenomics, expanded education for healthcare professionals, and the establishment of standardized guidelines for integrating these genetic insights into routine oncology practice. This could lead to more comprehensive treatment plans that account for individual patient variability.
| Aspect | Details |
|---|---|
| Focus | Integration of germline and somatic genomic data in oncology |
| Key Pharmacogenes | TPMT, UGT1A1, DPYD, and newly identified variants |
| Clinical Implications | Improved dosing recommendations and reduced adverse drug events |
| Collaboration | Involves oncologists, pharmacists, genetic counselors, and bioinformaticians |
| Future Research Needs | Explore clinical utility and standardize guidelines for implementation |
References
- 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)
- 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)
- 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)
- 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)
- Race and Pharmacogenomics-Personalized Medicine or Misguided Practice? - Christopher W Goodman;Allan S Brett - JAMA (2021)
- 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)
- 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)
- 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)
- 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)
- Sequencing of Charcot-Marie-Tooth disease genes in a toxic polyneuropathy. - Andreas S Beutler;Amit A Kulkarni;Rahul Kanwar;Christopher J Klein;Terry M Therneau;Rui Qin;Michaela S Banck;Ganesh K Boora;Kathryn J Ruddy;Yanhong Wu;Regenia L Smalley;Julie M Cunningham;Nguyet Anh Le-Lindqwister;Peter Beyerlein;Gary P Schroth;Anthony J Windebank;Stephan Züchner;Charles L Loprinzi - Annals of neurology (2014)
Literatures Citing This Work
- Genetic Influences in Cancer-Associated Myositis. - Karina Patasova;Ingrid E Lundberg;Marie Holmqvist - Arthritis & rheumatology (Hoboken, N.J.) (2023)
- Advances in Pharmacy Practice: A Look towards the Future. - Jeffrey Atkinson - Pharmacy (Basel, Switzerland) (2022)
- Characterization of Oncology Clinical Trials Using Germline Genetic Data. - Ashwin V Kammula;Alejandro A Schäffer;Padma Sheila Rajagopal - JAMA network open (2022)
- 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)
- 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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