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A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient

After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical car...

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Autores principales: Ali, Siraj M., Watson, Jessica, Wang, Kai, Chung, Jon H., McMahon, Caitlin, Ross, Jeffrey S., Dicke, Karel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899635/
https://www.ncbi.nlm.nih.gov/pubmed/27293397
http://dx.doi.org/10.1159/000443371
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author Ali, Siraj M.
Watson, Jessica
Wang, Kai
Chung, Jon H.
McMahon, Caitlin
Ross, Jeffrey S.
Dicke, Karel A.
author_facet Ali, Siraj M.
Watson, Jessica
Wang, Kai
Chung, Jon H.
McMahon, Caitlin
Ross, Jeffrey S.
Dicke, Karel A.
author_sort Ali, Siraj M.
collection PubMed
description After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients.
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spelling pubmed-48996352016-06-10 A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient Ali, Siraj M. Watson, Jessica Wang, Kai Chung, Jon H. McMahon, Caitlin Ross, Jeffrey S. Dicke, Karel A. Case Rep Oncol Published online: February, 2016 After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients. S. Karger AG 2016-02-18 /pmc/articles/PMC4899635/ /pubmed/27293397 http://dx.doi.org/10.1159/000443371 Text en Copyright © 2016 by S. Karger AG, Basel http://creativecommons.org/licenses/by-nc/4.0/ This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.
spellingShingle Published online: February, 2016
Ali, Siraj M.
Watson, Jessica
Wang, Kai
Chung, Jon H.
McMahon, Caitlin
Ross, Jeffrey S.
Dicke, Karel A.
A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient
title A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient
title_full A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient
title_fullStr A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient
title_full_unstemmed A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient
title_short A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient
title_sort combination of targeted therapy with chemotherapy backbone induces response in a treatment-resistant triple-negative mcl1-amplified metastatic breast cancer patient
topic Published online: February, 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899635/
https://www.ncbi.nlm.nih.gov/pubmed/27293397
http://dx.doi.org/10.1159/000443371
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