Journal
CANCERS
Volume 11, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/cancers11010105
Keywords
pan-HER inhibitor; triple-negative breast cancer
Categories
Funding
- Yang-Ming Branch of Taipei City Hospital [10601-62-020, 10701-62-030]
- Yen Tjing Ling Medical Foundation [CI-107-10]
- Ministry of Science and Technology, Taiwan [MOST 104-2628-B-075-001-MY3, 105-2314-B-075-044-MY3]
- Taipei Veterans General Hospital [V106C-101, V107C-025, V107C-016, V106D27-002-MY2-2]
- TVGH-NTUH Joint Research Program from Taipei Veterans General Hospital [VN106-07]
- Ministry of Health and Welfare, Executive Yuan, Taiwan [MOHW107-TDU-B-212-112015]
- National Taiwan-University Hospital
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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.
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