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.

背景：MDA-MB-231是三阴性乳腺癌（TNBC）细胞系，对酪氨酸激酶抑制剂（如拉帕替尼）具有抗性。拉帕替尼是公认的抗EGFR和抗Her2化合物。在这里，我们报告最无法治愈的乳腺癌类型TNBC细胞中lapatinibresistance的可能解释之一。

方法：使用蛋白质印迹法，我们观察到拉帕替尼处理的细胞增强了Akt的激活，Akt是在EGFR信号下游激活的致癌蛋白。

结果：拉帕替尼的抗EGFR活性将被Akt的持续激活所抵消。我们发现TNBC中的拉帕替尼耐药性可以通过使用Akt抑制剂来控制。此外，拉帕替尼增强的PI3K / Akt信号传导是确保MDAMB-231细胞生存力的替代途径。拉帕替尼可能还有未知靶标，需要进一步研究。

结论：该观察结果为克服对酪氨酸激酶抑制剂的耐药性开启了新的讨论，酪氨酸激酶抑制剂是治疗TNBC的关键挑战。