Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls?
The AKT protein kinase plays a central role in several interconnected molecular pathways involved in growth, apoptosis, angiogenesis, and cell metabolism. It thereby represents a therapeutic target, especially in hormone receptor-positive (HR) breast cancers, where the PI3K/AKT signaling pathway is...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13512 |
| _version_ | 1797503789496795136 |
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| author | Benoîte Mery Coralie Poulard Muriel Le Romancer Olivier Trédan |
| author_facet | Benoîte Mery Coralie Poulard Muriel Le Romancer Olivier Trédan |
| author_sort | Benoîte Mery |
| collection | DOAJ |
| description | The AKT protein kinase plays a central role in several interconnected molecular pathways involved in growth, apoptosis, angiogenesis, and cell metabolism. It thereby represents a therapeutic target, especially in hormone receptor-positive (HR) breast cancers, where the PI3K/AKT signaling pathway is largely hyperactivated. Moreover, resistance to therapeutic classes, including endocrine therapy, is associated with the constitutive activation of the PI3K/AKT pathway. Improved knowledge on the molecular mechanisms underlying resistance to endocrine therapy has led to the diversification of the therapeutic arsenal, notably with the development of PI3K and mTOR inhibitors, which are currently approved for the treatment of advanced HR-positive breast cancer patients. AKT itself constitutes a novel pharmacological target for which AKT inhibitors have been developed and tested in clinical trials. However, despite its pivotal role in cell survival and anti-apoptotic mechanisms, as well as in endocrine therapy resistance, few drugs have been developed and are available for clinical practice. The scope of the present review is to focus on the pivotal role of AKT in metastatic breast cancer through the analysis of its molecular features and to discuss clinical implications and remaining challenges in the treatment of HR-positive metastatic breast cancer. |
| first_indexed | 2024-03-10T03:55:21Z |
| format | Article |
| id | doaj.art-24a72b02f4214a8a8bab97a3c91830d0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:55:21Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-24a72b02f4214a8a8bab97a3c91830d02023-11-23T08:47:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241351210.3390/ijms222413512Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls?Benoîte Mery0Coralie Poulard1Muriel Le Romancer2Olivier Trédan3Medical Oncology Department, Centre Léon Bérard, F-69000 Lyon, FranceInserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, FranceInserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, FranceMedical Oncology Department, Centre Léon Bérard, F-69000 Lyon, FranceThe AKT protein kinase plays a central role in several interconnected molecular pathways involved in growth, apoptosis, angiogenesis, and cell metabolism. It thereby represents a therapeutic target, especially in hormone receptor-positive (HR) breast cancers, where the PI3K/AKT signaling pathway is largely hyperactivated. Moreover, resistance to therapeutic classes, including endocrine therapy, is associated with the constitutive activation of the PI3K/AKT pathway. Improved knowledge on the molecular mechanisms underlying resistance to endocrine therapy has led to the diversification of the therapeutic arsenal, notably with the development of PI3K and mTOR inhibitors, which are currently approved for the treatment of advanced HR-positive breast cancer patients. AKT itself constitutes a novel pharmacological target for which AKT inhibitors have been developed and tested in clinical trials. However, despite its pivotal role in cell survival and anti-apoptotic mechanisms, as well as in endocrine therapy resistance, few drugs have been developed and are available for clinical practice. The scope of the present review is to focus on the pivotal role of AKT in metastatic breast cancer through the analysis of its molecular features and to discuss clinical implications and remaining challenges in the treatment of HR-positive metastatic breast cancer.https://www.mdpi.com/1422-0067/22/24/13512estrogen-receptor-positive metastatic breast cancerendocrine resistanceserine/threonine kinase (AKT) signaling pathway |
| spellingShingle | Benoîte Mery Coralie Poulard Muriel Le Romancer Olivier Trédan Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls? International Journal of Molecular Sciences estrogen-receptor-positive metastatic breast cancer endocrine resistance serine/threonine kinase (AKT) signaling pathway |
| title | Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls? |
| title_full | Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls? |
| title_fullStr | Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls? |
| title_full_unstemmed | Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls? |
| title_short | Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls? |
| title_sort | targeting akt in er positive her2 negative metastatic breast cancer from molecular promises to real life pitfalls |
| topic | estrogen-receptor-positive metastatic breast cancer endocrine resistance serine/threonine kinase (AKT) signaling pathway |
| url | https://www.mdpi.com/1422-0067/22/24/13512 |
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