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Strategies to overcome trastuzumab resistance in HER2-overexpressing breast cancers: focus on new data from clinical trials.

ABSTRACT: Breast cancers over-express the human epidermal growth factor receptor 2 (HER2) in about 15% of patients. This transmembrane tyrosine kinase receptor activates downstream signaling pathways and leads to proliferation of cancer cells. Trastuzumab, an anti-HER2 monoclonal antibody, improves outcome in women with early and metastatic breast cancer. Resistance to trastuzumab involves the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway, truncation of the Her2 receptor or lack of immune response. The last decade has seen major advances in strategies to overcome resistance to trastuzumab. This includes the development of antibody-drug conjugates, dual HER2 inhibition strategies, inhibition of PI3K/mTOR pathway and development of modulators of immune checkpoints.

SUBMITTER: Lavaud P

PROVIDER: S-EPMC4243818 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Strategies to overcome trastuzumab resistance in HER2-overexpressing breast cancers: focus on new data from clinical trials.

Lavaud Pernelle P Andre Fabrice F

BMC medicine 20140812

Breast cancers over-express the human epidermal growth factor receptor 2 (HER2) in about 15% of patients. This transmembrane tyrosine kinase receptor activates downstream signaling pathways and leads to proliferation of cancer cells. Trastuzumab, an anti-HER2 monoclonal antibody, improves outcome in women with early and metastatic breast cancer. Resistance to trastuzumab involves the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway, truncation of the Her2 receptor or l ...[more]

PMID: 25285786

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