AI Article Synopsis
- Targeted therapies are effective for systemic cancer treatment but struggle with brain metastases, leading to poor control over these lesions.
- In breast cancer models, even with drug accumulation in brain metastases, they can bypass the effects of PI3K inhibitors, partly due to increased HER3 expression and activation.
- Blocking HER3 can sensitize resistant brain metastases to PI3K inhibitors, resulting in reduced tumor growth and improved survival in experimental models, suggesting new treatment strategies for certain breast cancer patients.
Article Abstract
Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of -amplified and/or -mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival. These data provide a mechanistic basis for therapeutic resistance in the brain microenvironment and identify translatable treatment strategies for -amplified and/or -mutant breast cancer brain metastases.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5917603 | PMC |
| http://dx.doi.org/10.1126/scitranslmed.aal4682 | DOI Listing |
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