Advances in targeting the WNT/13-catenin signaling pathway in cancer

被引：84

作者：

Chatterjee, Avradip ^{[1
]}

Paul, Sayan ^{[2
,6
]}

Bisht, Bharti ^{[3
]}

Bhattacharya, Shelley ^{[4
]}

Sivasubramaniam, Sudhakar ^{[2
]}

Paul, Manash K. ^{[5
]}

机构：

[1] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA

[2] Manonmaniam Sundaranar Univ, Dept Biotechnol, Tirunelveli 627012, Tamil Nadu, India

[3] Univ Calif Los Angeles, Dept Thorac Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA

[4] Visva Bharati, Dept Zool, Environm Toxicol Lab, Ctr Adv Studies, Santini Ketan 731235, W Bengal, India

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pulm & Crit Care Med, Los Angeles, CA 90095 USA

[6] Inst Stem Cell Sci & Regenerat Med InStem, Ctr Cardiovasc Biol & Dis, Bangalore 560065, Karnataka, India

来源：

DRUG DISCOVERY TODAY | 2022年 / 27卷 / 01期

关键词：

WNT; b-catenin signaling; Cancer; Inhibitors; Protein-small molecule interaction; Natural products; Drug design; Phase transition; Phosphorylation; Nuclear transport; Clinical trials; Artificial intelligence; Targeting protein-protein interaction; Challenges; SMALL-MOLECULE INHIBITORS; CATENIN NUCLEAR TRANSPORT; DISHEVELLED PDZ DOMAIN; SILICO DRUG DISCOVERY; BETA-CATENIN; CRYSTAL-STRUCTURE; URSOLIC ACID; BINDING; CELLS; AXIN;

D O I：

10.1016/j.drudis.2021.07.007

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

WNT/b-catenin signaling orchestrates various physiological processes, including embryonic development, growth, tissue homeostasis, and regeneration. Abnormal WNT/b-catenin signaling is associated with various cancers and its inhibition has shown effective antitumor responses. In this review, we discuss the pathway, potential targets for the development of WNT/b-catenin inhibitors, available inhibitors, and their specific molecular interactions with the target proteins. We also discuss inhibitors that are in clinical trials and describe potential new avenues for therapeutically targeting the WNT/b-catenin pathway. Furthermore, we introduce emerging strategies, including artificial intelligence (AI)-assisted tools and technology based actionable approaches, to translate WNT/b-catenin inhibitors to the clinic for cancer therapy.

引用

页码：82 / 101

页数：20

共 122 条

[1] Liquid-Liquid Phase Separation in Disease [J].

Alberti, Simon ;

Dormann, Dorothee .

ANNUAL REVIEW OF GENETICS, VOL 53, 2019, 53 :171-+

[2] Nuclear Regulation of Wnt/β-Catenin Signaling: It's a Complex Situation [J].

Anthony, Christin C. ;

Robbins, David J. ;

Ahmed, Yashi ;

Lee, Ethan .

GENES, 2020, 11 (08) :1-11

[3] Distinct Spatiotemporally Dynamic Wnt-Secreting Niches Regulate Proximal Airway Regeneration and Aging [J].

Aros, Cody J. ;

Vijayaraj, Preethi ;

Pantoja, Carla J. ;

Bisht, Bharti ;

Meneses, Luisa K. ;

Sandlin, Jenna M. ;

Tse, Jonathan A. ;

Chen, Michelle W. ;

Purkayastha, Arunima ;

Shia, David W. ;

Sucre, Jennifer Ms ;

Rickabaugh, Tammy M. ;

Vladar, Eszter K. ;

Paul, Manash K. ;

Gomperts, Brigitte N. .

CELL STEM CELL, 2020, 27 (03) :413-+

[4] High-Throughput Drug Screening Identifies a Potent Wnt Inhibitor that Promotes Airway Basal Stem Cell Homeostasis [J].

Aros, Cody J. ;

Paul, Manash K. ;

Pantoja, Carla J. ;

Bisht, Bharti ;

Meneses, Luisa K. ;

Vijayaraj, Preethi ;

Sandlin, Jenna M. ;

France, Bryan ;

Tse, Jonathan A. ;

Chen, Michelle W. ;

Shia, David W. ;

Rickabaugh, Tammy M. ;

Damoiseaux, Robert ;

Gomperts, Brigitte N. .

CELL REPORTS, 2020, 30 (07) :2055-2064

[5] 'WNT-er is coming': WNT signalling in chronic lung diseases [J].

Baarsma, H. A. ;

Konigshoff, M. .

THORAX, 2017, 72 (08) :746-759

[6] Artificial Intelligence in Drug Discovery: Into the Great Wide Open [J].

Bajorath, Jurgen ;

Kearnes, Steven ;

Walters, W. Patrick ;

Meanwell, Nicholas A. ;

Georg, Gunda I. ;

Wang, Shaomeng .

JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (16) :8651-8652

[7] Rapid and site-specific deep phosphoproteome profiling by data-independent acquisition without the need for spectral libraries [J].

Bekker-Jensen, Dorte B. ;

Bernhardt, Oliver M. ;

Hogrebe, Alexander ;

Martinez-Val, Ana ;

Verbeke, Lynn ;

Gandhi, Tejas ;

Kelstrup, Christian D. ;

Reiter, Lukas ;

Olsen, Jesper V. .

NATURE COMMUNICATIONS, 2020, 11 (01)

[8] Ran GTPase: A Key Player in Tumor Progression and Metastasis [J].

Boudhraa, Zied ;

Carmona, Euridice ;

Provencher, Diane ;

Mes-Masson, Anne-Marie .

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2020, 8

[9] Allosteric inhibitor of β-catenin selectively targets oncogenic Wnt signaling in colon cancer [J].

Cheltsov, Anton ;

Nomura, Natsuko ;

Yenugonda, Venkata M. ;

Roper, Jatin ;

Mukthavaram, Rajesh ;

Jiang, Pengfei ;

Her, Nam-Gu ;

Babic, Ivan ;

Kesari, Santosh ;

Nurmemmedov, Elmar .

SCIENTIFIC REPORTS, 2020, 10 (01)

[10] Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer [J].

Chen, Baozhi ;

Dodge, Michael E. ;

Tang, Wei ;

Lu, Jianming ;

Ma, Zhiqiang ;

Fan, Chih-Wei ;

Wei, Shuguang ;

Hao, Wayne ;

Kilgore, Jessica ;

Williams, Noelle S. ;

Roth, Michael G. ;

Amatruda, James F. ;

Chen, Chuo ;

Lum, Lawrence .

NATURE CHEMICAL BIOLOGY, 2009, 5 (02) :100-107

← 1 2 3 4 5 6 7 8 9 10 →