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Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia
SIMPLE SUMMARY: Acute myeloid leukemia (AML) is a predominately fatal blood cancer. For a period of forty years, treatment options for AML remained relatively stagnant. Recently, multiple new agents have been approved. In this review, we discuss considerations surrounding the use of these newly appr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471378/ https://www.ncbi.nlm.nih.gov/pubmed/34572873 http://dx.doi.org/10.3390/cancers13184646 |
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author | Ahmadmehrabi, Khashayar Haque, Ali R. Aleem, Ahmed Griffiths, Elizabeth A. Roloff, Gregory W. |
author_facet | Ahmadmehrabi, Khashayar Haque, Ali R. Aleem, Ahmed Griffiths, Elizabeth A. Roloff, Gregory W. |
author_sort | Ahmadmehrabi, Khashayar |
collection | PubMed |
description | SIMPLE SUMMARY: Acute myeloid leukemia (AML) is a predominately fatal blood cancer. For a period of forty years, treatment options for AML remained relatively stagnant. Recently, multiple new agents have been approved. In this review, we discuss considerations surrounding the use of these newly approved therapies. We outline the molecular profiles of AML disease status and highlight subsets of patients for whom therapies are best suited based on available data. ABSTRACT: Despite considerable growth in our understanding of the heterogeneous biology and pathogenesis of acute myeloid leukemia (AML) in recent decades, for nearly forty years, little progress was gained in the realm of novel therapeutics. Since 2017, however, nine agents have been FDA-approved for patients with AML in both the upfront and relapsed/refractory (R/R) settings. Most of these compounds function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival. They have been approved both as single agents and in combination with conventional or reduced-intensity conventional chemotherapeutics. In this article, we review the molecular landscape of de novo vs. R/R AML and highlight the potential translational impact of defined molecular disease subsets. We also highlight several recent agents that have entered the therapeutic armamentarium and where they fit in the AML treatment landscape, with a focus on FLT3 inhibitors, IDH1 and IDH2 inhibitors, and venetoclax. Finally, we close with a survey of two promising novel agents under investigation that are poised to enter the mainstream clinical arena in the near future. |
format | Online Article Text |
id | pubmed-8471378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84713782021-09-27 Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia Ahmadmehrabi, Khashayar Haque, Ali R. Aleem, Ahmed Griffiths, Elizabeth A. Roloff, Gregory W. Cancers (Basel) Review SIMPLE SUMMARY: Acute myeloid leukemia (AML) is a predominately fatal blood cancer. For a period of forty years, treatment options for AML remained relatively stagnant. Recently, multiple new agents have been approved. In this review, we discuss considerations surrounding the use of these newly approved therapies. We outline the molecular profiles of AML disease status and highlight subsets of patients for whom therapies are best suited based on available data. ABSTRACT: Despite considerable growth in our understanding of the heterogeneous biology and pathogenesis of acute myeloid leukemia (AML) in recent decades, for nearly forty years, little progress was gained in the realm of novel therapeutics. Since 2017, however, nine agents have been FDA-approved for patients with AML in both the upfront and relapsed/refractory (R/R) settings. Most of these compounds function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival. They have been approved both as single agents and in combination with conventional or reduced-intensity conventional chemotherapeutics. In this article, we review the molecular landscape of de novo vs. R/R AML and highlight the potential translational impact of defined molecular disease subsets. We also highlight several recent agents that have entered the therapeutic armamentarium and where they fit in the AML treatment landscape, with a focus on FLT3 inhibitors, IDH1 and IDH2 inhibitors, and venetoclax. Finally, we close with a survey of two promising novel agents under investigation that are poised to enter the mainstream clinical arena in the near future. MDPI 2021-09-16 /pmc/articles/PMC8471378/ /pubmed/34572873 http://dx.doi.org/10.3390/cancers13184646 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Ahmadmehrabi, Khashayar Haque, Ali R. Aleem, Ahmed Griffiths, Elizabeth A. Roloff, Gregory W. Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia |
title | Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia |
title_full | Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia |
title_fullStr | Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia |
title_full_unstemmed | Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia |
title_short | Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia |
title_sort | targeted therapies for the evolving molecular landscape of acute myeloid leukemia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471378/ https://www.ncbi.nlm.nih.gov/pubmed/34572873 http://dx.doi.org/10.3390/cancers13184646 |
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