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Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL
SIMPLE SUMMARY: The phosphoinositide 3-kinase (PI3K) is a family of kinases that play a key role in the biology of chronic lymphocytic leukemia (CLL). Inhibitors of PI3K demonstrated efficacy in the treatment of CLL, associated with significant adverse events that limited the clinical use of this dr...
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/PMC7999552/ https://www.ncbi.nlm.nih.gov/pubmed/33805745 http://dx.doi.org/10.3390/cancers13061280 |
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author | Guarente, Valerio Sportoletti, Paolo |
author_facet | Guarente, Valerio Sportoletti, Paolo |
author_sort | Guarente, Valerio |
collection | PubMed |
description | SIMPLE SUMMARY: The phosphoinositide 3-kinase (PI3K) is a family of kinases that play a key role in the biology of chronic lymphocytic leukemia (CLL). Inhibitors of PI3K demonstrated efficacy in the treatment of CLL, associated with significant adverse events that limited the clinical use of this drugs. In this review, we underlined the relevance of PI3K inhibitors in CLL, we collected recent data about the use of these molecules in clinical practice and in clinical trial discussing strategies for the management of adverse events, which could help to improve the use of these therapies in the treatment of CLL. ABSTRACT: Chronic lymphocytic leukemia (CLL) shows constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of the B-cell receptor (BCR) signaling. PI3K inhibitors have been evaluated in CLL therapy, bringing a new treatment opportunity for patients with this disease. Despite the proven therapeutic efficacy, the use of approved PI3K inhibitors is limited by severe immune-mediated toxicities and given the availability of other more tolerable agents. This article reviews the relevance of PI3K signaling and pharmacologic inhibition in CLL. Data on efficacy and toxicity of PI3K inhibitors are also presented, as well as strategies for overcoming barriers for their clinical use in CLL treatment. |
format | Online Article Text |
id | pubmed-7999552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79995522021-03-28 Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL Guarente, Valerio Sportoletti, Paolo Cancers (Basel) Review SIMPLE SUMMARY: The phosphoinositide 3-kinase (PI3K) is a family of kinases that play a key role in the biology of chronic lymphocytic leukemia (CLL). Inhibitors of PI3K demonstrated efficacy in the treatment of CLL, associated with significant adverse events that limited the clinical use of this drugs. In this review, we underlined the relevance of PI3K inhibitors in CLL, we collected recent data about the use of these molecules in clinical practice and in clinical trial discussing strategies for the management of adverse events, which could help to improve the use of these therapies in the treatment of CLL. ABSTRACT: Chronic lymphocytic leukemia (CLL) shows constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of the B-cell receptor (BCR) signaling. PI3K inhibitors have been evaluated in CLL therapy, bringing a new treatment opportunity for patients with this disease. Despite the proven therapeutic efficacy, the use of approved PI3K inhibitors is limited by severe immune-mediated toxicities and given the availability of other more tolerable agents. This article reviews the relevance of PI3K signaling and pharmacologic inhibition in CLL. Data on efficacy and toxicity of PI3K inhibitors are also presented, as well as strategies for overcoming barriers for their clinical use in CLL treatment. MDPI 2021-03-13 /pmc/articles/PMC7999552/ /pubmed/33805745 http://dx.doi.org/10.3390/cancers13061280 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Guarente, Valerio Sportoletti, Paolo Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL |
title | Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL |
title_full | Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL |
title_fullStr | Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL |
title_full_unstemmed | Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL |
title_short | Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL |
title_sort | lessons, challenges and future therapeutic opportunities for pi3k inhibition in cll |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999552/ https://www.ncbi.nlm.nih.gov/pubmed/33805745 http://dx.doi.org/10.3390/cancers13061280 |
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