Abstract
Women with ErbB2-positive breast cancer have a poor prognosis, and frequently, chemotherapy treatment is ineffective. The ErbB2-targeted antibody trastuzumab improves survival when given with chemotherapy to patients with ErbB2-overexpressing metastatic disease, but treatment is not curative, and primary resistance is common. Postulated mechanisms of action for trastuzumab include immune-mediated cytotoxicity and receptor downmodulation. A study in this issue of Cancer Cell suggests that trastuzumab causes rapid activation of the PTEN lipid phosphatase, which in turn downregulates the phosphatidylinositol 3'-kinase (PI3K) pathway. Resistance to trastuzumab occurs when PTEN function is lost, suggesting that PTEN activation is a critical component of the therapeutic effect.
MeSH terms
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Antibodies, Monoclonal / metabolism
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Antibodies, Monoclonal / therapeutic use*
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / therapeutic use*
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Breast Neoplasms / diagnosis
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Enzyme Activation
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Female
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Genes, Tumor Suppressor
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Humans
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PTEN Phosphohydrolase
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoric Monoester Hydrolases / metabolism*
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Receptor, ErbB-2 / metabolism*
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Signal Transduction / physiology
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Trastuzumab
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Tumor Suppressor Proteins / metabolism*
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Tumor Suppressor Proteins
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Phosphatidylinositol 3-Kinases
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Receptor, ErbB-2
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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PTEN protein, human
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Trastuzumab