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Cancer epigenetics in clinical practice.
Literature Information
| DOI | 10.3322/caac.21765 |
|---|---|
| PMID | 36512337 |
| Journal | CA: a cancer journal for clinicians |
| Impact Factor | 232.4 |
| JCR Quartile | Q1 |
| Publication Year | 2023 |
| Times Cited | 114 |
| Keywords | DNA methylation, cancer, epigenetic biomarkers, epigenetic drugs, epigenetics |
| Literature Type | Journal Article, Review |
| ISSN | 0007-9235 |
| Pages | 376-424 |
| Issue | 73(4) |
| Authors | Veronica Davalos, Manel Esteller |
TL;DR
This review discusses the role of epigenetic modifications, particularly DNA methylation and histone marks, in cancer development and progression, emphasizing their potential as diagnostic and therapeutic tools. It highlights the clinical applications of epigenetic biomarkers and FDA-approved epigenetic drugs, underscoring the significance of targeting the reversible nature of epigenetic changes in cancer treatment.
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DNA methylation · cancer · epigenetic biomarkers · epigenetic drugs · epigenetics
Abstract
Cancer development is driven by the accumulation of alterations affecting the structure and function of the genome. Whereas genetic changes disrupt the DNA sequence, epigenetic alterations contribute to the acquisition of hallmark tumor capabilities by regulating gene expression programs that promote tumorigenesis. Shifts in DNA methylation and histone mark patterns, the two main epigenetic modifications, orchestrate tumor progression and metastasis. These cancer-specific events have been exploited as useful tools for diagnosis, monitoring, and treatment choice to aid clinical decision making. Moreover, the reversibility of epigenetic modifications, in contrast to the irreversibility of genetic changes, has made the epigenetic machinery an attractive target for drug development. This review summarizes the most advanced applications of epigenetic biomarkers and epigenetic drugs in the clinical setting, highlighting commercially available DNA methylation-based assays and epigenetic drugs already approved by the US Food and Drug Administration.
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Primary Questions Addressed
- What are the most promising epigenetic biomarkers currently being used in clinical practice for cancer diagnosis?
- How do DNA methylation and histone modifications specifically influence tumorigenesis and cancer progression?
- In what ways can epigenetic therapies be integrated into existing cancer treatment protocols to enhance patient outcomes?
- What challenges do researchers face in translating epigenetic findings from the laboratory to clinical applications?
- How do the regulatory pathways governing epigenetic modifications differ between various types of cancer?
Key Findings
Key Insights
Research Background and Objectives:
The study addresses the critical role of epigenetics in cancer development, which is characterized by changes in the genome's structure and function. Unlike genetic mutations that alter DNA sequences, epigenetic modifications, such as DNA methylation and histone alterations, influence gene expression without changing the underlying genetic code. The objective of the research is to explore how these epigenetic changes contribute to tumorigenesis and how they can be leveraged in clinical practice for diagnosis, treatment, and monitoring of cancer.Main Methods and Findings:
The review synthesizes current knowledge on the mechanisms by which epigenetic alterations drive cancer progression and metastasis. It discusses the patterns of DNA methylation and histone modifications that are specific to various cancers. Additionally, it highlights the development and application of epigenetic biomarkers in clinical settings, including commercially available DNA methylation-based assays. The review also covers epigenetic drugs that have received approval from the US Food and Drug Administration (FDA), showcasing their potential in cancer therapy. The findings indicate that the reversible nature of epigenetic modifications provides a unique opportunity for therapeutic intervention in cancer management.Core Conclusions:
The study concludes that epigenetic alterations play a significant role in cancer biology by regulating gene expression patterns that facilitate tumor growth and spread. These alterations not only serve as important biomarkers for cancer diagnosis and prognosis but also represent promising targets for therapeutic strategies. With FDA-approved epigenetic drugs already in use, the integration of epigenetic insights into clinical practice holds the potential to revolutionize cancer treatment paradigms.Research Significance and Impact:
The insights provided by this review underscore the importance of epigenetics in the understanding and management of cancer. By highlighting the clinical applications of epigenetic biomarkers and therapies, the study emphasizes the potential for improved patient outcomes through personalized medicine approaches. The ability to target reversible epigenetic modifications can lead to novel treatment options that are less invasive than traditional therapies. This research has significant implications for the future of oncology, as it encourages the incorporation of epigenetic assessments into routine clinical practice, which could enhance diagnostic accuracy and treatment efficacy in cancer care.
Literatures Citing This Work
- The BRD4 inhibitor JQ1 augments the antitumor efficacy of abemaciclib in preclinical models of gastric carcinoma. - Mei Feng;Hao Xu;Wenyuan Zhou;Yisheng Pan - Journal of experimental & clinical cancer research : CR (2023)
- Systematic pan-cancer analysis identifies gasdermin B as an immunological and prognostic biomarker for kidney renal clear cell carcinoma. - Xuehe Liu;Feiyan Xie;Jin Ding;Suhua Li;Jixi Li - Frontiers in oncology (2023)
- Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics. - Maxime Janin;Veronica Davalos;Manel Esteller - Cancer metastasis reviews (2023)
- An overview of DNA methylation markers for early detection of gastric cancer: current status, challenges, and prospects. - Ying Xue;Chao Huang;Bing Pei;ZhenZhen Wang;Yanmiao Dai - Frontiers in genetics (2023)
- The Bivalent Bromodomain Inhibitor MT-1 Inhibits Prostate Cancer Growth. - Sanjeev Shukla;Carlos Riveros;Mohammed Al-Toubat;Jonathan Chardon-Robles;Teruko Osumi;Samuel Serrano;Adam M Kase;Joachim L Petit;Nathalie Meurice;Justyna Gleba;John A Copland;Jay Chauhan;Steven Fletcher;K C Balaji - Cancers (2023)
- Challenges and Opportunities in Developing Targeted Therapies for Triple Negative Breast Cancer. - Abygail G Chapdelaine;Gongqin Sun - Biomolecules (2023)
- BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach. - Yassire Oubaddou;Mohamed Oukabli;Salma Fenniche;Abderrahim Elktaibi;Mohamed Reda Elochi;Abderrahmane Al Bouzidi;Zineb Qmichou;Nadia Dakka;Caroline Diorio;Antje Richter;Youssef Bakri;Rabii Ameziane El Hassani - Genes (2023)
- A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers. - Yanmiao Dai;Hui Li;Qianqian Wu;Jie Wang;Kai Wang;Sujuan Fei;Bing Pei;Lishuang Song;Guangxia Chen;Yong Ma;Chenjing Xia;Shangmin Xiong;Minxue Zheng;Ying Xue;Guodong Zhao;Hongwei Xu - Neoplasia (New York, N.Y.) (2023)
- Function and regulation of RGS family members in solid tumours: a comprehensive review. - Chenglong Yang;Xiaoyuan Zhang;Xiaowen Yang;Fuming Lian;Zongrun Sun;Yongming Huang;Wenzhi Shen - Cell communication and signaling : CCS (2023)
- Repression of LSD1 potentiates homologous recombination-proficient ovarian cancer to PARP inhibitors through down-regulation of BRCA1/2 and RAD51. - Lei Tao;Yue Zhou;Xiangyu Pan;Yuan Luo;Jiahao Qiu;Xia Zhou;Zhiqian Chen;Yan Li;Lian Xu;Yang Zhou;Zeping Zuo;Chunqi Liu;Liang Wang;Xiaocong Liu;Xinyu Tian;Na Su;Zhengnan Yang;Yu Zhang;Kun Gou;Na Sang;Huan Liu;Jiao Zou;Yuzhou Xiao;Xi Zhong;Jing Xu;Xinyu Yang;Kai Xiao;Yanyang Liu;Shengyong Yang;Yong Peng;Junhong Han;Xiaobo Cen;Yinglan Zhao - Nature communications (2023)
... (104 more literatures)
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