Colorectal Cancer: Pathogenesis and Targeted Therapy

被引:4
作者
Li, Jingyuan [1 ,2 ]
Pan, Jiashu [1 ,2 ]
Wang, Lisheng [3 ,4 ]
Ji, Guang [1 ,2 ]
Dang, Yanqi [1 ,2 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Digest Dis, China Canada Ctr Res Digest Dis, Shanghai, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, State Key Lab Integrat & Innovat Class Formula & M, Shanghai, Peoples R China
[3] Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada
[4] Univ Ottawa, China Canada Ctr Res Digest Dis, Ottawa, ON, Canada
来源
MEDCOMM | 2025年 / 6卷 / 03期
基金
中国国家自然科学基金;
关键词
colorectal cancer; genetics; epigenetics; tumor metabolism; molecular mechanisms; targeted therapy; FATTY-ACID SYNTHASE; HISTONE DEACETYLASE INHIBITOR; EPITHELIAL-MESENCHYMAL TRANSITION; INFLAMMATORY-BOWEL-DISEASE; ABERRANT CRYPT FOCI; CELL-CYCLE ARREST; ATP CITRATE LYASE; COLON-CANCER; ANTITUMOR-ACTIVITY; LIPID-METABOLISM;
D O I
10.1002/mco2.70127
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Colorectal cancer (CRC) ranks among the most prevalent malignant neoplasms globally. A growing body of evidence underscores the pivotal roles of genetic alterations and dysregulated epigenetic modifications in the pathogenesis of CRC. In recent years, the reprogramming of tumor cell metabolism has been increasingly acknowledged as a hallmark of cancer. Substantial evidence suggests a crosstalk between tumor cell metabolic reprogramming and epigenetic modifications, highlighting a complex interplay between metabolism and the epigenetic genome that warrants further investigation. Biomarkers associated with the pathogenesis and metabolic characteristics of CRC hold significant clinical implications. Nevertheless, elucidating the genetic, epigenetic, and metabolic landscapes of CRC continues to pose considerable challenges. Here, we attempt to summarize the key genes driving the onset and progression of CRC and the related epigenetic regulators, clarify the roles of gene expression and signaling pathways in tumor metabolism regulation, and explore the potential crosstalk between epigenetic events and tumor metabolic reprogramming, providing a comprehensive mechanistic explanation for the malignant progression of CRC. Finally, by integrating reliable targets from genetics, epigenetics, and metabolic processes that hold promise for translation into clinical practice, we aim to offer more strategies to overcome the bottlenecks in CRC treatment.
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页数:29
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共 273 条
[1]   Synergistic Effect of Epigenetic Inhibitors Decitabine and Suberoylanilide Hydroxamic Acid on Colorectal Cancer In vitro [J].
Abou Najem, Sonia ;
Khawaja, Ghada ;
Hodroj, Mohammad Hassan ;
Rizk, Sandra .
CURRENT MOLECULAR PHARMACOLOGY, 2019, 12 (04) :281-300
[2]   The Lipogenesis Pathway as a Cancer Target [J].
Abramson, Hanley N. .
JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (16) :5615-5638
[3]   ACETYLATION + METHYLATION OF HISTONES + THEIR POSSIBLE ROLE IN REGULATION OF RNA SYNTHESIS [J].
ALLFREY, VG ;
FAULKNER, R ;
MIRSKY, AE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1964, 51 (05) :786-+
[4]   Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance [J].
Amodio, Vito ;
Lamba, Simona ;
Chila, Rosaria ;
Cattaneo, Chiara M. ;
Mussolin, Benedetta ;
Corti, Giorgio ;
Rospo, Giuseppe ;
Berrino, Enrico ;
Tripodo, Claudio ;
Pisati, Federica ;
Bartolini, Alice ;
Aquilano, Maria Costanza ;
Marsoni, Silvia ;
Mauri, Gianluca ;
Marchio, Caterina ;
Abrignani, Sergio ;
Di Nicolantonio, Federica ;
Germano, Giovanni ;
Bardelli, Alberto .
CANCER CELL, 2023, 41 (01) :196-+
[5]   Global Histone H4 Acetylation and HDAC2 Expression in Colon Adenoma and Carcinoma [J].
Ashktorab, Hassan ;
Belgrave, Kevin ;
Hosseinkhah, Fatemeh ;
Brim, Hassan ;
Nouraie, Mehdi ;
Takkikto, Mikiko ;
Hewitt, Steve ;
Lee, Edward L. ;
Dashwood, R. H. ;
Smoot, Duane .
DIGESTIVE DISEASES AND SCIENCES, 2009, 54 (10) :2109-2117
[6]   Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study [J].
Azad, Nilofer S. ;
el-Khoueiry, Anthony ;
Yin, Jun ;
Oberg, Ann L. ;
Flynn, Patrick ;
Adkins, Douglas ;
Sharma, Anup ;
Weisenberger, Daniel J. ;
Brown, Thomas ;
Medvari, Prakriti ;
Jones, Peter A. ;
Easwaran, Hariharan ;
Kamel, Ihab ;
Bahary, Nathan ;
Kim, George ;
Picus, Joel ;
Pitot, Henry C. ;
Erlichman, Charles ;
Donehower, Ross ;
Shen, Hui ;
Laird, Peter W. ;
Piekarz, Richard ;
Baylin, Stephen ;
Ahuja, Nita .
ONCOTARGET, 2017, 8 (21) :35326-35338
[7]   Long Interspersed Element-1 Methylation Level as a Prognostic Biomarker in Gastrointestinal Cancers [J].
Baba, Yoshifumi ;
Yagi, Taisuke ;
Sawayama, Hiroshi ;
Hiyoshi, Yukiharu ;
Ishimoto, Takatsugu ;
Iwatsuki, Masaaki ;
Miyamoto, Yuji ;
Yoshida, Naoya ;
Baba, Hideo .
DIGESTION, 2018, 97 (01) :26-30
[8]   DNA mismatch repair in cancer [J].
Baretti, Marina ;
Le, Dung T. .
PHARMACOLOGY & THERAPEUTICS, 2018, 189 :45-62
[9]   Nuclear expression of histone deacetylases and their histone modifications predicts clinical outcome in colorectal cancer [J].
Benard, Anne ;
Goossens-Beumer, Ines J. ;
van Hoesel, Anneke Q. ;
Horati, Hamed ;
de Graaf, Wouter ;
Putter, Hein ;
Zeestraten, Eliane C. M. ;
Liefers, Gerrit-Jan ;
van de Velde, Cornelis J. H. ;
Kuppen, Peter J. K. .
HISTOPATHOLOGY, 2015, 66 (02) :270-282
[10]   Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase [J].
Bilen, Ozlem ;
Ballantyne, Christie M. .
CURRENT ATHEROSCLEROSIS REPORTS, 2016, 18 (10)