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.