Breast (Edinburgh), 2015-10, Vol.24 (5), p.548-555
2015
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- Autor(en) / Beteiligte
- Titel
- Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway
- Ist Teil von
- Breast (Edinburgh), 2015-10, Vol.24 (5), p.548-555
- Ort / Verlag
- Netherlands: Elsevier Ltd
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Abstract 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-9776eISSN: 1532-3080DOI: 10.1016/j.breast.2015.06.002Titel-ID: cdi_proquest_miscellaneous_1719420433
- Format
- –
- Schlagworte
- Antibodies, Monoclonal, Humanized - administration & dosage, Antineoplastic Combined Chemotherapy Protocols - therapeutic use, Breast cancer, Breast Neoplasms - drug therapy, Breast Neoplasms - metabolism, Clinical Trials as Topic, Drug Resistance, Neoplasm, Everolimus, Everolimus - administration & dosage, Female, Hematology, Oncology and Palliative Medicine, HER2, Humans, Molecular Targeted Therapy, mTOR, Paclitaxel - administration & dosage, Phosphatidylinositol 3-Kinase - antagonists & inhibitors, Phosphatidylinositol 3-Kinase - metabolism, Proto-Oncogene Proteins c-akt - antagonists & inhibitors, Proto-Oncogene Proteins c-akt - metabolism, Receptor, ErbB-2 - metabolism, Resistance, Signal Transduction, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - metabolism, Trastuzumab - administration & dosage, Vinblastine - administration & dosage, Vinblastine - analogs & derivatives