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      The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy

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          Abstract

          Histone modifications are key factors in chromatin packaging, and are responsible for gene regulation during cell fate determination and development. Abnormal alterations in histone modifications potentially affect the stability of the genome and disrupt gene expression patterns, leading to many diseases, including cancer. In recent years, mounting evidence has shown that various histone modifications altered by aberrantly expressed modifier enzymes contribute to tumor development and metastasis through the induction of epigenetic, transcriptional, and phenotypic changes. In this review, we will discuss the existing histone modifications, both well-studied and rare ones, and their roles in solid tumors and hematopoietic cancers, to identify the molecular pathways involved and investigate targeted therapeutic drugs to reorganize the chromatin and enhance cancer treatment efficiency. Finally, clinical inhibitors of histone modifications are summarized to better understand the developmental stage of cancer therapy in using these drugs to inhibit the histone modification enzymes.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Cancer Statistics, 2017.

            Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2017)
            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the "epidemic of diagnosis." Over the past decade of available data, the overall cancer incidence rate (2004-2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017;67:7-30. © 2017 American Cancer Society.
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              Regulation of chromatin by histone modifications.

              Andrew Bannister, Tony Kouzarides (2011)
              Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just beginning to be understood. However, it is clear that histone modifications play fundamental roles in most biological processes that are involved in the manipulation and expression of DNA. Here, we describe the known histone modifications, define where they are found genomically and discuss some of their functional consequences, concentrating mostly on transcription where the majority of characterisation has taken place.
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                Author and article information

                Contributors
                Yan Wang
                Journal
                Journal ID (nlm-ta): J Natl Cancer Cent
                Journal ID (iso-abbrev): J Natl Cancer Cent
                Title: Journal of the National Cancer Center
                Publisher: Elsevier
                ISSN (Print): 2096-8663
                ISSN (Electronic): 2667-0054
                Publication date PMC-release: 28 September 2022
                Publication date Collection: December 2022
                Publication date (Electronic): 28 September 2022
                Volume: 2
                Issue: 4
                Pages: 277-290
                Affiliations
                [0001]Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                Author notes
                [* ]Corresponding author. yanwang@ 123456cicams.ac.cn
                [†]

                These authors contributed equally to this work.

                Article
                Publisher Item ID: S2667-0054(22)00064-3
                DOI: 10.1016/j.jncc.2022.09.002
                PMC ID: 11256729
                SO-VID: ae0a60c0-ca9a-4acd-b055-643ecdca2b2d
                Copyright © © 2022 Chinese National Cancer Center. Published by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 7 August 2022
                Date revision received : 19 September 2022
                Date accepted : 26 September 2022
                Categories
                Subject: Review

                Keywords: histone modification,tumorigenesis,histone modifier enzyme inhibitor
                Data availability:
                Keywords: histone modification, tumorigenesis, histone modifier enzyme inhibitor

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