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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Letter to the Editor

Lapatinib as a Dual Tyrosine Kinase Inhibitor Unexpectedly Activates Akt in MDA-MB-231 Triple-Negative Breast Cancer Cells

Author(s): Parham Jabbarzadeh Kaboli * and King-Hwa Ling

Volume 17, Issue 8, 2020

Page: [1060 - 1063] Pages: 4

DOI: 10.2174/1570180817666200212125658

Abstract

Background: MDA-MB-231 is a Triple-Negative Breast Cancer (TNBC) cell line, which is resistant to tyrosine kinase inhibitors, such as lapatinib. Lapatinib is well-recognized as an anti- EGFR and anti-Her2 compound. Here, we report one of the possible explanations for lapatinibresistance in TNBC cells, the most incurable type of breast cancer.

Methods: Using western blotting, we have observed that lapatinib-treated cells enhanced activation of Akt, an oncogenic protein activated at downstream of EGFR signaling.

Results: Anti-EGFR activity of Lapatinib would be counteracted with sustained activation of Akt. We found lapatinib-resistance in TNBC can be managed by administering Akt inhibitors. Further, lapatinib enhanced PI3K/Akt signaling is an alternative pathway to ensure the viability of MDAMB- 231 cells. There might also be unknown targets for lapatinib, which needs further investigation.

Conclusion: This observation opens up a new discussion on overcoming resistance to tyrosine kinase inhibitors, a key challenge in treating TNBC.

Keywords: Breast Cancer, TNBC, Lapatinib, Akt, Resistance, EGFR.

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