Recent progress in TGF-? inhibitors for cancer therapy - 17/01/21

Doi : 10.1016/j.biopha.2020.111046

Cheng-Yi Huang ^a,^b,^{^{1
These authors contributed equally to this work.}}, Chih-Ling Chung ^a,^{^{1
These authors contributed equally to this work.}}, Tsung-Hui Hu ^c,^{^{1
These authors contributed equally to this work.}}, Jih-Jung Chen ^d,^e, Pei-Feng Liu ^f, Chun-Lin Chen ^a,^g,^h,⁎
^a Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, ROC
^b Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan, ROC
^c Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan, ROC
^d Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan, ROC
^e Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
^f Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan ROC
^g Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan ROC
^h Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan ROC

^⁎Corresponding author at: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, ROC.Department of Biological SciencesNational Sun Yat-sen UniversityKaohsiung80424Taiwan, ROC

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Highlights

•	Summary of the basic studies, patents, and clinical trials inhibiting TGF-β signalling, a critical pathway in tumorigenesis and fibrosis.
•	Small molecular inhibitors and neutralizing antibodies against TGF-β signaling are potential strategies for cancer therapy.
•	Natural products and repurposed drugs should continue to be major resources for screening TGF-β inhibitors.
•	The future prospect of new sources and mechanisms of TGF-β inhibitors are discussed in this review.

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Abstract

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that is involved in proliferation, metastasis, and many other important processes in malignancy. Inhibitors targeting TGF-β have been considered by pharmaceutical companies for cancer therapy, and some of them are in clinical trial now. Unfortunately, several of these programs have recently been relinquished, and most companies that remain in the contest are progressing slowly and cautiously. This review summarizes the TGF-β signal transduction pathway, its roles in oncogenesis and fibrotic diseases, and advancements in antibodies and small-molecule inhibitors of TGF-β.

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Keywords : Small-molecule inhibitor, Cancer therapy, TGF-β inhibitor, Endocytosis, Lipid raft

Plan

Introduction

ASOs against TGF-β mRNA

Ligand traps and monoclonal neutralizing antibodies

In sclerosis or fibrosis

In cancer

Vaccine-based strategy

Small molecule inhibiting receptor kinase activity

In HCC

In glioma

In pancreatic cancer (PAC)

In NSCLC

Intracellular peptide aptamers

Potential strategies for TGF-β inhibition and future perspectives

Conclusion

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Article 111046- février 2021 Retour au numéro

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Recent progress in TGF-? inhibitors for cancer therapy - 17/01/21

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