HER2-positive breast cancer : available targeted agents and biomarkers for therapy response
In the last decade, the targeted therapy of breast cancer became part of routine clinical protocols all over the globe. Options in today's targeted therapy include hormonal therapy and the modulation of the EGFR/HER-pathway. Of the four HER receptors, HER2 is the target of currently used treatment strategies. HER2 activates multiple intracellular pathways via RAS, RAF and PI3K. We give a comprehensive summary of approved monoclonal antibodies and tyrosine kinase inhibitors acting over HER2, including trastuzumab, lapatinib and pertuzumab. We elaborate on their mechanism of action and on clinical trials behind their approval. Agents in third phase clinical studies (neratinib, afatinib) are also described. We give a brief overview of agents currently in phase I and phase II studies; these are acting over the PI3K pathway, over IGFR1 and over HSP90. Furthermore, currently validated negative biomarkers (markers predicting lack of response) in clinical use are also summarized. Finally, the major bottlenecks of clinical application including tumor heterogeneity and the high diversity of clinical studies are discussed. For a breakthrough we will need to identify new positive biomarkers of therapy response.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:57 |
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| Enthalten in: |
Magyar onkologia - 57(2013), 3 vom: 10. Sept., Seite 147-56 |
| Sprache: |
Ungarisch |
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| Weiterer Titel: |
HER2-pozitív emlőtumorok célzott terápiájában alkalmazott szerek és a terápiás válasz előrejelzése |
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| Beteiligte Personen: |
Mihály, Zsuzsanna [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.01.2014 Date Revised 03.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
MagyOnkol.2013.57.3.147 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM231530692 |
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| 520 | |a In the last decade, the targeted therapy of breast cancer became part of routine clinical protocols all over the globe. Options in today's targeted therapy include hormonal therapy and the modulation of the EGFR/HER-pathway. Of the four HER receptors, HER2 is the target of currently used treatment strategies. HER2 activates multiple intracellular pathways via RAS, RAF and PI3K. We give a comprehensive summary of approved monoclonal antibodies and tyrosine kinase inhibitors acting over HER2, including trastuzumab, lapatinib and pertuzumab. We elaborate on their mechanism of action and on clinical trials behind their approval. Agents in third phase clinical studies (neratinib, afatinib) are also described. We give a brief overview of agents currently in phase I and phase II studies; these are acting over the PI3K pathway, over IGFR1 and over HSP90. Furthermore, currently validated negative biomarkers (markers predicting lack of response) in clinical use are also summarized. Finally, the major bottlenecks of clinical application including tumor heterogeneity and the high diversity of clinical studies are discussed. For a breakthrough we will need to identify new positive biomarkers of therapy response | ||
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