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Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain?

ABSTRACT: The brain is the most common site of first metastasis for patients with HER2-positive breast cancer treated with HER2-targeting drugs. However, the development of effective therapies for breast cancer brain metastases (BCBM) is limited by an incomplete understanding of the mechanisms governing drug sensitivity in the central nervous system. Pharmacodynamic data from patients and in vivo models suggest that inadequate drug penetration across the "blood-tumor" barrier is not the whole story. Using HER2-positive BCBMs as a case study, we highlight recent data from orthotopic brain metastasis models that implicate brain-specific drug resistance mechanisms in BCBMs and suggest a translational research paradigm to guide drug development for treatment of BCBMs. Clin Cancer Res; 24(8); 1795-804. ©2018 AACR.

SUBMITTER: Kabraji S

PROVIDER: S-EPMC5899637 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain?

Kabraji Sheheryar S Ni Jing J Lin Nancy U NU Xie Shaozhen S Winer Eric P EP Zhao Jean J JJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20180206 8

The brain is the most common site of first metastasis for patients with HER2-positive breast cancer treated with HER2-targeting drugs. However, the development of effective therapies for breast cancer brain metastases (BCBM) is limited by an incomplete understanding of the mechanisms governing drug sensitivity in the central nervous system. Pharmacodynamic data from patients and <i>in vivo</i> models suggest that inadequate drug penetration across the "blood-tumor" barrier is not the whole story ...[more]

PMID: 29437794

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