Parham Jabbarzadeh Kaboli * and King-Hwa Ling Pages 1060 - 1063 ( 4 )
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.
Breast Cancer, TNBC, Lapatinib, Akt, Resistance, EGFR.
Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, Selangor, Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, Selangor