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Co-targeting CDK4/6...
Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer
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- Alves, Carla L. (författare)
- University of Southern Denmark
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- Ehmsen, Sidse (författare)
- University of Southern Denmark,Odense University Hospital
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- Terp, Mikkel G. (författare)
- University of Southern Denmark
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- Portman, Neil (författare)
- Garvan Institute of Medical Research,University of New South Wales
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- Tuttolomondo, Martina (författare)
- University of Southern Denmark
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- Gammelgaard, Odd L. (författare)
- University of Southern Denmark
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- Hundebøl, Monique F. (författare)
- University of Southern Denmark
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- Kaminska, Kamila (författare)
- Lund University,Lunds universitet,Molekylära behandlingsstrategier vid bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Molecular therapeutics in breast cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Johansen, Lene E. (författare)
- University of Southern Denmark
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- Bak, Martin (författare)
- Hospital of South West Jutland, Esbjerg
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- Honeth, Gabriella (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Molekylära behandlingsstrategier vid bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Molecular therapeutics in breast cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Bosch, Ana (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Molekylära behandlingsstrategier vid bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Molecular therapeutics in breast cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Lim, Elgene (författare)
- Garvan Institute of Medical Research,University of New South Wales
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- Ditzel, Henrik J. (författare)
- University of Southern Denmark,Odense University Hospital
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(creator_code:org_t)
- 2021-08-25
- 2021
- Engelska.
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have shown impressive efficacy in estrogen receptor-positive advanced breast cancer. However, most patients will eventually experience disease progression on this combination, underscoring the need for effective subsequent treatments or better initial therapies. Here, we show that triple inhibition with fulvestrant, CDK4/6i and AKT inhibitor (AKTi) durably impairs growth of breast cancer cells, prevents progression and reduces metastasis of tumor xenografts resistant to CDK4/6i-fulvestrant combination or fulvestrant alone. Importantly, switching from combined fulvestrant and CDK4/6i upon resistance to dual combination with AKTi and fulvestrant does not prevent tumor progression. Furthermore, triple combination with AKTi significantly inhibits growth of patient-derived xenografts resistant to combined CDK4/6i and fulvestrant. Finally, high phospho-AKT levels in metastasis of breast cancer patients treated with a combination of CDK4/6i and endocrine therapy correlates with shorter progression-free survival. Our findings support the clinical development of ER, CDK4/6 and AKT co-targeting strategies following progression on CDK4/6i and endocrine therapy combination, and in tumors exhibiting high phospho-AKT levels, which are associated with worse clinical outcome.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Alves, Carla L.
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Ehmsen, Sidse
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Terp, Mikkel G.
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Portman, Neil
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Tuttolomondo, Ma ...
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Gammelgaard, Odd ...
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visa fler...
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Hundebøl, Moniqu ...
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Kaminska, Kamila
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Johansen, Lene E ...
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Bak, Martin
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Honeth, Gabriell ...
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Bosch, Ana
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Lim, Elgene
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Ditzel, Henrik J ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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Lunds universitet