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Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?
SIMPLE SUMMARY: Since the identification of a large variety of biomarkers in B cell malignancies as being driving factors for tumor progression and patient prognosis, their targeting may confer valuable options for the treatment of these diseases. Over the past 20 years, the permanent development of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775488/ https://www.ncbi.nlm.nih.gov/pubmed/36551511 http://dx.doi.org/10.3390/cancers14246026 |
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author | Tannoury, Mariana Garnier, Delphine Susin, Santos A. Bauvois, Brigitte |
author_facet | Tannoury, Mariana Garnier, Delphine Susin, Santos A. Bauvois, Brigitte |
author_sort | Tannoury, Mariana |
collection | PubMed |
description | SIMPLE SUMMARY: Since the identification of a large variety of biomarkers in B cell malignancies as being driving factors for tumor progression and patient prognosis, their targeting may confer valuable options for the treatment of these diseases. Over the past 20 years, the permanent development of a multitude of inhibitors acting on survival-associated biomarkers has made it into clinical evaluation in B lymphoid tumors. Although certain drugs approved by the US Food and Drug Administration improve clinical outcome, some patients do not respond and others relapse. This review summarizes the current state-of-the-art, provides a summary of new, safer, more selective inhibitors currently under evaluation in clinical trials, and highlights the emerging positioning of metabolic drugs in tumor B cell biology as a promising strategy to be translated into clinical practice. ABSTRACT: Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton’s tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders. |
format | Online Article Text |
id | pubmed-9775488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97754882022-12-23 Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next? Tannoury, Mariana Garnier, Delphine Susin, Santos A. Bauvois, Brigitte Cancers (Basel) Review SIMPLE SUMMARY: Since the identification of a large variety of biomarkers in B cell malignancies as being driving factors for tumor progression and patient prognosis, their targeting may confer valuable options for the treatment of these diseases. Over the past 20 years, the permanent development of a multitude of inhibitors acting on survival-associated biomarkers has made it into clinical evaluation in B lymphoid tumors. Although certain drugs approved by the US Food and Drug Administration improve clinical outcome, some patients do not respond and others relapse. This review summarizes the current state-of-the-art, provides a summary of new, safer, more selective inhibitors currently under evaluation in clinical trials, and highlights the emerging positioning of metabolic drugs in tumor B cell biology as a promising strategy to be translated into clinical practice. ABSTRACT: Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton’s tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders. MDPI 2022-12-07 /pmc/articles/PMC9775488/ /pubmed/36551511 http://dx.doi.org/10.3390/cancers14246026 Text en © 2022 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 Tannoury, Mariana Garnier, Delphine Susin, Santos A. Bauvois, Brigitte Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next? |
title | Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next? |
title_full | Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next? |
title_fullStr | Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next? |
title_full_unstemmed | Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next? |
title_short | Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next? |
title_sort | current status of novel agents for the treatment of b cell malignancies: what’s coming next? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775488/ https://www.ncbi.nlm.nih.gov/pubmed/36551511 http://dx.doi.org/10.3390/cancers14246026 |
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