Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer
Up to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/12/2922 |
| _version_ | 1797530503999389696 |
|---|---|
| author | Ryan W. Holloway Paola A. Marignani |
| author_facet | Ryan W. Holloway Paola A. Marignani |
| author_sort | Ryan W. Holloway |
| collection | DOAJ |
| description | Up to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target of rapamycin (mTOR) pathway activity and a metabolic shift to glycolysis. Although inhibitors targeting the HER2 receptor have been successful in treating HER2-positive breast cancer, anti-HER2 therapy is associated with a high risk of recurrence and drug resistance due to stimulation of the PI3K-Akt-mTOR signaling pathway and glycolysis. Combination therapies against HER2 with inhibition of mTOR improve clinical outcomes compared to HER2 inhibition alone. Here, we review the role of the HER2 receptor, mTOR pathway, and glycolysis in HER2-positive breast cancer, along with signaling mechanisms and the efficacy of treatment strategies of HER2-positive breast cancer. |
| first_indexed | 2024-03-10T10:29:55Z |
| format | Article |
| id | doaj.art-0c45c61a556b41d3b86b3d3785707ccf |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:29:55Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0c45c61a556b41d3b86b3d3785707ccf2023-11-21T23:42:40ZengMDPI AGCancers2072-66942021-06-011312292210.3390/cancers13122922Targeting mTOR and Glycolysis in HER2-Positive Breast CancerRyan W. Holloway0Paola A. Marignani1Department of Biochemistry & Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Biochemistry & Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, CanadaUp to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target of rapamycin (mTOR) pathway activity and a metabolic shift to glycolysis. Although inhibitors targeting the HER2 receptor have been successful in treating HER2-positive breast cancer, anti-HER2 therapy is associated with a high risk of recurrence and drug resistance due to stimulation of the PI3K-Akt-mTOR signaling pathway and glycolysis. Combination therapies against HER2 with inhibition of mTOR improve clinical outcomes compared to HER2 inhibition alone. Here, we review the role of the HER2 receptor, mTOR pathway, and glycolysis in HER2-positive breast cancer, along with signaling mechanisms and the efficacy of treatment strategies of HER2-positive breast cancer.https://www.mdpi.com/2072-6694/13/12/2922mTORglycolysisHER2-positive breast cancer2-deoxyglucosetrastuzumabHerceptin |
| spellingShingle | Ryan W. Holloway Paola A. Marignani Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer Cancers mTOR glycolysis HER2-positive breast cancer 2-deoxyglucose trastuzumab Herceptin |
| title | Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer |
| title_full | Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer |
| title_fullStr | Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer |
| title_full_unstemmed | Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer |
| title_short | Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer |
| title_sort | targeting mtor and glycolysis in her2 positive breast cancer |
| topic | mTOR glycolysis HER2-positive breast cancer 2-deoxyglucose trastuzumab Herceptin |
| url | https://www.mdpi.com/2072-6694/13/12/2922 |
| work_keys_str_mv | AT ryanwholloway targetingmtorandglycolysisinher2positivebreastcancer AT paolaamarignani targetingmtorandglycolysisinher2positivebreastcancer |