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A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors

Multiple myeloma (MM) is a blood cancer that derives from plasma cells (PCs), which will accumulate in the bone marrow (BM). Over time, several drugs have been developed to treat this disease that is still uncurable. The therapies used to treat the disease target immune activity, inhibit proteasome...

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Autores principales: Raimondi, Vincenzo, Iannozzi, Nicolas Thomas, Burroughs-Garcìa, Jessica, Toscani, Denise, Storti, Paola, Giuliani, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Open Exploration 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9446161/
https://www.ncbi.nlm.nih.gov/pubmed/36071980
http://dx.doi.org/10.37349/etat.2022.00095
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author Raimondi, Vincenzo
Iannozzi, Nicolas Thomas
Burroughs-Garcìa, Jessica
Toscani, Denise
Storti, Paola
Giuliani, Nicola
author_facet Raimondi, Vincenzo
Iannozzi, Nicolas Thomas
Burroughs-Garcìa, Jessica
Toscani, Denise
Storti, Paola
Giuliani, Nicola
author_sort Raimondi, Vincenzo
collection PubMed
description Multiple myeloma (MM) is a blood cancer that derives from plasma cells (PCs), which will accumulate in the bone marrow (BM). Over time, several drugs have been developed to treat this disease that is still uncurable. The therapies used to treat the disease target immune activity, inhibit proteasome activity, and involve the use of monoclonal antibodies. However, MM is a highly heterogeneous disease, in fact, there are several mutations in signaling pathways that are particularly important for MM cell biology and that are possible therapeutic targets. Indeed, some studies suggest that MM is driven by mutations within the rat sarcoma virus (RAS) signaling cascade, which regulates cell survival and proliferation. The RAS/proto-oncogene, serine/threonine kinase (RAF)/mitogen-activated extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway is deregulated in several cancers, for which drugs have been developed to inhibit these pathways. In addition to the signaling pathways, the disease implements mechanisms to ensure the survival and consequently a high replicative capacity. This strategy consists in the deregulation of apoptosis. In particular, some cases of MM show overexpression of anti-apoptotic proteins belonging to the B cell lymphoma 2 (BCL-2) family that represent a possible druggable target. Venetoclax is an anti-BCL-2 molecule used in hematological malignancies that may be used in selected MM patients based on their molecular profile. We focused on the possible effects in MM of off-label drugs that are currently used for other cancers with the same molecular characteristics. Their use, combined with the current treatments, could be a good strategy against MM.
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spelling pubmed-94461612022-09-06 A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors Raimondi, Vincenzo Iannozzi, Nicolas Thomas Burroughs-Garcìa, Jessica Toscani, Denise Storti, Paola Giuliani, Nicola Explor Target Antitumor Ther Review Multiple myeloma (MM) is a blood cancer that derives from plasma cells (PCs), which will accumulate in the bone marrow (BM). Over time, several drugs have been developed to treat this disease that is still uncurable. The therapies used to treat the disease target immune activity, inhibit proteasome activity, and involve the use of monoclonal antibodies. However, MM is a highly heterogeneous disease, in fact, there are several mutations in signaling pathways that are particularly important for MM cell biology and that are possible therapeutic targets. Indeed, some studies suggest that MM is driven by mutations within the rat sarcoma virus (RAS) signaling cascade, which regulates cell survival and proliferation. The RAS/proto-oncogene, serine/threonine kinase (RAF)/mitogen-activated extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway is deregulated in several cancers, for which drugs have been developed to inhibit these pathways. In addition to the signaling pathways, the disease implements mechanisms to ensure the survival and consequently a high replicative capacity. This strategy consists in the deregulation of apoptosis. In particular, some cases of MM show overexpression of anti-apoptotic proteins belonging to the B cell lymphoma 2 (BCL-2) family that represent a possible druggable target. Venetoclax is an anti-BCL-2 molecule used in hematological malignancies that may be used in selected MM patients based on their molecular profile. We focused on the possible effects in MM of off-label drugs that are currently used for other cancers with the same molecular characteristics. Their use, combined with the current treatments, could be a good strategy against MM. Open Exploration 2022 2022-08-31 /pmc/articles/PMC9446161/ /pubmed/36071980 http://dx.doi.org/10.37349/etat.2022.00095 Text en © The Author(s) 2022. https://creativecommons.org/licenses/by/4.0/This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Raimondi, Vincenzo
Iannozzi, Nicolas Thomas
Burroughs-Garcìa, Jessica
Toscani, Denise
Storti, Paola
Giuliani, Nicola
A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors
title A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors
title_full A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors
title_fullStr A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors
title_full_unstemmed A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors
title_short A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors
title_sort personalized molecular approach in multiple myeloma: the possible use of raf/ras/mek/erk and bcl-2 inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9446161/
https://www.ncbi.nlm.nih.gov/pubmed/36071980
http://dx.doi.org/10.37349/etat.2022.00095
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