کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6169812 | 1251181 | 2015 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway](/preview/png/6169812.png)
- While therapies targeting HER2 have improved outcomes, patients develop resistance.
- Determining molecular mechanisms of resistance to HER2 therapies may improve outcomes.
- Targeting the PI3K/Akt/mTOR pathway may be an effective therapeutic strategy.
Human epidermal growth factor receptor 2 (HER2) overexpression occurs in up to 30% of breast cancers and is a marker of aggressive disease. While HER2-targeted therapies have improved outcomes in these tumors, resistance to these agents develops in a large proportion of patients. Determining molecular mechanisms underlying resistance might help improve outcomes for patients with HER2-positive disease by allowing development of strategies to overcome resistance. Activation of signaling pathways involving the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway might contribute to the development of resistance to HER2-targeted therapies. Several inhibitors of this pathway are under investigation in this disease setting and phase 3 data for everolimus in combination with trastuzumab and chemotherapy in trastuzumab-refractory, advanced disease are promising. In this review, molecular mechanisms underlying resistance to HER2-targeted therapies are considered and evidence for strategies to manage resistance is evaluated, including the use of inhibitors of the PI3K/Akt/mTOR pathway.
Journal: The Breast - Volume 24, Issue 5, October 2015, Pages 548-555