Next Article in Journal
Connexins and Integrins in Exosomes
Previous Article in Journal
Transfer of Extracellular Vesicle-Associated-RNAs Induces Drug Resistance in ALK-Translocated Lung Adenocarcinoma
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Cancers 2019, 11(1), 105; https://doi.org/10.3390/cancers11010105

Varlitinib Downregulates HER/ERK Signaling and Induces Apoptosis in Triple Negative Breast Cancer Cells

1
Comprehensive Breast Health Center, Taipei Veterans General Hospital, No.201, Sec.2, Shih-Pai Rd., Taipei 112, Taiwan
2
Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, No.201, Sec.2, Shih-Pai Rd., Taipei 112, Taiwan
3
School of Medicine, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei 112, Taiwan
4
Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, No.201, Sec.2, Shih-Pai Rd., Taipei 112, Taiwan
5
Department of Pathology, Show Chwan Memorial Hospital, No.542, Sec.1, Chung-Shan Rd., Changhua City 500, Taiwan
6
School of Medicine, Fu Jen Catholic University, No.510, Zhong-zheng Rd., Xin-zhuang Dist., New Taipei City 24205, Taiwan
7
Division of Hematology and Oncology, Department of Medicine, Yang-Ming Branch of Taipei City Hospital, No.145, Zhengzhou Rd., Datong Dist., Taipei 103, Taiwan
8
Department of Medical Genetics, National Taiwan University Hospital, No.7, Chung-Shan South Rd., Taipei 100, Taiwan
9
Graduate institute of medical genomics and proteomics, National Taiwan University, No.1, Sec.4, Roosevelt Rd., Taipei 106, Taiwan
10
Hematology/Oncology, Tri-Service General Hospital, National Defense Medical Center, No.325, Sec.2, Cheng-gong Rd., Taipei 114, Taiwan
11
Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan
*
Author to whom correspondence should be addressed.
Received: 29 December 2018 / Accepted: 15 January 2019 / Published: 17 January 2019
Full-Text   |   PDF [4113 KB, uploaded 17 January 2019]   |  

Abstract

Triple-negative breast cancer (TNBC) is a complex disease associated with the aggressive phenotype and poor prognosis. TNBC harbors heterogeneous molecular subtypes with no approved specific targeted therapy. It has been reported that HER receptors are overexpressed in breast cancer including TNBC. In this study, we evaluated the efficacy of varlitinib, a reversible small molecule pan-HER inhibitor in TNBC. Our results showed that varlitinib reduced cell viability and induced cell apoptosis in most TNBC cell lines but not in MDA-MB-231 cells. MEK and ERK inhibition overcame resistance to varlitinib in MDA-MB-231 cells. Varlitinib inhibited HER signaling which led to inhibition of migration, invasion and mammosphere formation of TNBC cells as well as significant suppression of tumor growth of MDA-MB-468 xenograft mouse model. In summary, these results suggest that HER signaling plays an important role in TNBC progression and that pan-HER inhibition is potentially an effective treatment for TNBC patients. View Full-Text
Keywords: pan-HER inhibitor; triple-negative breast cancer pan-HER inhibitor; triple-negative breast cancer
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Liu, C.-Y.; Chu, P.-Y.; Huang, C.-T.; Chen, J.-L.; Yang, H.-P.; Wang, W.-L.; Lau, K.-Y.; Lee, C.-H.; Lan, T.-Y.; Huang, T.-T.; Lin, P.-H.; Dai, M.-S.; Tseng, L.-M. Varlitinib Downregulates HER/ERK Signaling and Induces Apoptosis in Triple Negative Breast Cancer Cells. Cancers 2019, 11, 105.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top