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

[51] Ursolic acid and its natural derivative corosolic acid suppress the proliferation of APC-mutated colon cancer cells through promotion of β-catenin degradation [J].

Kim, Joo-Hyun ;

Kim, Young Ho ;

Song, Gyu-Yong ;

Kim, Dong-Eun ;

Jeong, Yong-Joo ;

Liu, Kwang-Hyeon ;

Chung, Young-Hwa ;

Oh, Sangtaek .

FOOD AND CHEMICAL TOXICOLOGY, 2014, 67 :87-95

[52] Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939 [J].

Kirby, Christina A. ;

Cheung, Atwood ;

Fazal, Aleem ;

Shultz, Michael D. ;

Stams, Travis .

ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, 2012, 68 :115-118

[53] Not All Wnt Activation Is Equal: Ligand-Dependent versus Ligand-Independent Wnt Activation in Colorectal Cancer [J].

Kleeman, Sam O. ;

Leedham, Simon J. .

CANCERS, 2020, 12 (11) :1-16

[54] Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors [J].

Krishnamurthy, Nithya ;

Kurzrock, Razelle .

CANCER TREATMENT REVIEWS, 2018, 62 :50-60

[55] A Novel Tankyrase Small-Molecule Inhibitor Suppresses APC Mutation-Driven Colorectal Tumor Growth [J].

Lau, Ted ;

Chan, Emily ;

Callow, Marinella ;

Waaler, Jo ;

Boggs, Jason ;

Blake, Robert A. ;

Magnuson, Steven ;

Sambrone, Amy ;

Schutten, Melissa ;

Firestein, Ron ;

Machon, Ondrej ;

Korinek, Vladimir ;

Choo, Edna ;

Diaz, Dolores ;

Merchant, Mark ;

Polakis, Paul ;

Holsworth, Daniel D. ;

Krauss, Stefan ;

Costa, Mike .

CANCER RESEARCH, 2013, 73 (10) :3132-3144

[56] Cell Signaling by Receptor Tyrosine Kinases [J].

Lemmon, Mark A. ;

Schlessinger, Joseph .

CELL, 2010, 141 (07) :1117-1134

[57]

Li Y, 2019, PLOS ONE, V14, pXXX

[58] Small molecules from natural products targeting the Wnt/β-catenin pathway as a therapeutic strategy [J].

Liu, Dan ;

Chen, Lin ;

Zhao, Hui ;

Vaziri, Nosratola D. ;

Ma, Shuang-Cheng ;

Zhao, Ying-Yong .

BIOMEDICINE & PHARMACOTHERAPY, 2019, 117

[59] Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974 [J].

Liu, Jun ;

Pan, Shifeng ;

Hsieh, Mindy H. ;

Ng, Nicholas ;

Sun, Fangxian ;

Wang, Tao ;

Kasibhatla, Shailaja ;

Schuller, Alwin G. ;

Li, Allen G. ;

Cheng, Dai ;

Li, Jie ;

Tompkins, Celin ;

Pferdekamper, AnneMarie ;

Steffy, Auzon ;

Cheng, Jane ;

Kowal, Colleen ;

Van Phung ;

Guo, Guirong ;

Wang, Yan ;

Graham, Martin P. ;

Flynn, Shannon ;

Brenner, J. Chad ;

Li, Chun ;

Villarroel, M. Cristina ;

Schultz, Peter G. ;

Wu, Xu ;

McNamara, Peter ;

Sellers, William R. ;

Petruzzelli, Lilli ;

Boral, Anthony L. ;

Seidel, H. Martin ;

McLaughlin, Margaret E. ;

Che, Jianwei ;

Carey, Thomas E. ;

Vanasse, Gary ;

Harris, Jennifer L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (50) :20224-20229

[60] Tetrandrine, a Chinese plant-derived alkaloid, is a potential candidate for cancer chemotherapy [J].

Liu, Ting ;

Liu, Xin ;

Li, Wenhua .

ONCOTARGET, 2016, 7 (26) :40800-40815

← 1 2 3 4 5 6 7 8 9 10 →