Kinase inhibition in multiple myeloma: current scenario and clinical perspectives

Detalhes bibliográficos
Autor(a) principal: Barreto, Igor Valentim
Data de Publicação: 2022
Outros Autores: Machado, Caio Bezerra, Almeida, Davi Benevides, Pessoa, Flávio Melo Cunha de Pinho, Gadelha, Renan Brito, Pantoja, Laudreísa da Costa, Oliveira, Deivide de Sousa, Ribeiro, Rodrigo Monteiro, Lopes, Germison Silva, Moraes Filho, Manoel Odorico de, Moraes, Maria Elisabete Amaral de, Khayat, André Salim, Oliveira, Edivaldo Herculano Corrêa de, Nunes, Caroline Aquino Moreira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
Texto Completo: https://patua.iec.gov.br/handle/iec/4669
Resumo: Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease. The treatments currently available cannot cure the patient, but only extend their lifespan, and the main and most effective alternative is autologous hematopoietic stem cell transplantation, but not every patient is eligible, often due to age and pre-existing comorbidities. In this context, the search for new therapies that can bring better results to patients is of utmost importance. Protein tyrosine kinases (PTKs) are involved in several biological processes, such as cell growth regulation and proliferation, thus, mutations that affect their functionality can have a great impact on crucial molecular pathways in the cells, leading to tumorigenesis. In the past couple of decades, the use of small-molecule inhibitors, which include tyrosine kinase inhibitors (TKIs), has been a hallmark in the treatment of hematological malignancies, and MM patients may also benefit from TKI-based treatment strategies. In this review, we seek to understand the applicability of TKIs used in MM clinical trials in the last 10 years.
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spelling Barreto, Igor ValentimMachado, Caio BezerraAlmeida, Davi BenevidesPessoa, Flávio Melo Cunha de PinhoGadelha, Renan BritoPantoja, Laudreísa da CostaOliveira, Deivide de SousaRibeiro, Rodrigo MonteiroLopes, Germison SilvaMoraes Filho, Manoel Odorico deMoraes, Maria Elisabete Amaral deKhayat, André SalimOliveira, Edivaldo Herculano Corrêa deNunes, Caroline Aquino Moreira2022-10-03T17:15:48Z2022-10-03T17:15:48Z2022BARRETO, Igor Valentim et al. Kinase inhibition in multiple myeloma: current scenario and clinical perspectives. Pharmaceutics, v. 14, n. 9, p. 1-16, Aug. 2022. DOI: 10.3390/pharmaceutics14091784. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506264/pdf/pharmaceutics-14-01784.pdf.1999-4923https://patua.iec.gov.br/handle/iec/466910.3390/pharmaceutics14091784Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease. The treatments currently available cannot cure the patient, but only extend their lifespan, and the main and most effective alternative is autologous hematopoietic stem cell transplantation, but not every patient is eligible, often due to age and pre-existing comorbidities. In this context, the search for new therapies that can bring better results to patients is of utmost importance. Protein tyrosine kinases (PTKs) are involved in several biological processes, such as cell growth regulation and proliferation, thus, mutations that affect their functionality can have a great impact on crucial molecular pathways in the cells, leading to tumorigenesis. In the past couple of decades, the use of small-molecule inhibitors, which include tyrosine kinase inhibitors (TKIs), has been a hallmark in the treatment of hematological malignancies, and MM patients may also benefit from TKI-based treatment strategies. In this review, we seek to understand the applicability of TKIs used in MM clinical trials in the last 10 years.This study was supported by Brazilian funding agencies: Coordination for the Improvement of Higher Education Personnel (CAPES), National Council of Technological and Scientific Development (CNPq grant number 404213/2021-9), Cearense Foundation of Scientific and Technological Support (FUNCAP grant number P20-0171-00078.01.00/20)Federal University of Ceará. Department of Medicine, Drug Research and Development Center. Pharmacogenetics Laboratory. Fortaleza, CE, Brazil.Federal University of Ceará. Department of Medicine, Drug Research and Development Center. Pharmacogenetics Laboratory. Fortaleza, CE, Brazil.Unichristus University Center. Faculty of Biomedicine. Fortaleza, CE, Brazil.Federal University of Ceará. Department of Medicine, Drug Research and Development Center. Pharmacogenetics Laboratory. Fortaleza, CE, Brazil.Federal University of Ceará. Department of Medicine, Drug Research and Development Center. Pharmacogenetics Laboratory. Fortaleza, CE, Brazil.Federal University of Pará. Department of Biological Sciences. Oncology Research Center. Belém, PA, Brazil.Fortaleza General Hospital. Department of Hematology. Fortaleza, CE, Brazil.Fortaleza General Hospital. Department of Hematology. Fortaleza, CE, Brazil.César Cals General Hospital. Department of Hematology. Fortaleza, CE, Brazil.Federal University of Ceará. Department of Medicine, Drug Research and Development Center. Pharmacogenetics Laboratory. Fortaleza, CE, Brazil.Federal University of Ceará. Department of Medicine, Drug Research and Development Center. Pharmacogenetics Laboratory. Fortaleza, CE, Brazil.Federal University of Pará. Department of Biological Sciences. Oncology Research Center. Belém, PA, Brazil.Federal University of Pará. Faculty of Natural Sciences. Institute of Exact and Natural Sciences. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Citogenômica e Mutagênese Ambiental. Ananindeua, PA, Brasil.Federal University of Ceará. Department of Medicine, Drug Research and Development Center. Pharmacogenetics Laboratory. Fortaleza, CE, Brazil / Federal University of Pará. Department of Biological Sciences. Oncology Research Center. Belém, PA, Brazil / Ceará State University - Itaperi Campus. Northeast Biotechnology Network. Fortaleza, CE, Brazil.engMDPIKinase inhibition in multiple myeloma: current scenario and clinical perspectivesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleNeoplasias / sangueMieloma Múltiplo / tratamento farmacológicoProteínas do Mieloma / análiseibrutinibe / tratamento farmacológicoTirosina QuinaseQuinases da Família srcinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALKinase inhibition in multiple myeloma: current scenario and clinical perspectives.pdfKinase inhibition in multiple myeloma: current scenario and clinical perspectives.pdfapplication/pdf1156419https://patua.iec.gov.br/bitstreams/90951422-9f15-4660-9ccd-d3efdf7642e4/downloade5f8c324ccf4dd5de483dd1ffa7fdaa9MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/4b1ab417-d85a-4a12-8be3-c58ff9be961a/download11832eea31b16df8613079d742d61793MD52TEXTKinase inhibition in multiple myeloma: current scenario and clinical perspectives.pdf.txtKinase inhibition in multiple myeloma: current scenario and clinical perspectives.pdf.txtExtracted texttext/plain81871https://patua.iec.gov.br/bitstreams/6e288028-594a-422c-9db2-97044ac38800/download3642713fa7130e84ac6d25fad3720be2MD55THUMBNAILKinase inhibition in multiple myeloma: current scenario and clinical perspectives.pdf.jpgKinase inhibition in multiple myeloma: current scenario and clinical perspectives.pdf.jpgGenerated Thumbnailimage/jpeg5350https://patua.iec.gov.br/bitstreams/6dbe5d1e-929a-481e-afd9-dbe122e76de7/download07456fd44a13567e916828e36132547bMD56iec/46692022-10-20 22:09:35.454oai:patua.iec.gov.br:iec/4669https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-20T22:09:35Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)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
dc.title.pt_BR.fl_str_mv Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
title Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
spellingShingle Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
Barreto, Igor Valentim
Neoplasias / sangue
Mieloma Múltiplo / tratamento farmacológico
Proteínas do Mieloma / análise
ibrutinibe / tratamento farmacológico
Tirosina Quinase
Quinases da Família src
title_short Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
title_full Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
title_fullStr Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
title_full_unstemmed Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
title_sort Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
author Barreto, Igor Valentim
author_facet Barreto, Igor Valentim
Machado, Caio Bezerra
Almeida, Davi Benevides
Pessoa, Flávio Melo Cunha de Pinho
Gadelha, Renan Brito
Pantoja, Laudreísa da Costa
Oliveira, Deivide de Sousa
Ribeiro, Rodrigo Monteiro
Lopes, Germison Silva
Moraes Filho, Manoel Odorico de
Moraes, Maria Elisabete Amaral de
Khayat, André Salim
Oliveira, Edivaldo Herculano Corrêa de
Nunes, Caroline Aquino Moreira
author_role author
author2 Machado, Caio Bezerra
Almeida, Davi Benevides
Pessoa, Flávio Melo Cunha de Pinho
Gadelha, Renan Brito
Pantoja, Laudreísa da Costa
Oliveira, Deivide de Sousa
Ribeiro, Rodrigo Monteiro
Lopes, Germison Silva
Moraes Filho, Manoel Odorico de
Moraes, Maria Elisabete Amaral de
Khayat, André Salim
Oliveira, Edivaldo Herculano Corrêa de
Nunes, Caroline Aquino Moreira
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Barreto, Igor Valentim
Machado, Caio Bezerra
Almeida, Davi Benevides
Pessoa, Flávio Melo Cunha de Pinho
Gadelha, Renan Brito
Pantoja, Laudreísa da Costa
Oliveira, Deivide de Sousa
Ribeiro, Rodrigo Monteiro
Lopes, Germison Silva
Moraes Filho, Manoel Odorico de
Moraes, Maria Elisabete Amaral de
Khayat, André Salim
Oliveira, Edivaldo Herculano Corrêa de
Nunes, Caroline Aquino Moreira
dc.subject.decsPrimary.pt_BR.fl_str_mv Neoplasias / sangue
Mieloma Múltiplo / tratamento farmacológico
Proteínas do Mieloma / análise
ibrutinibe / tratamento farmacológico
Tirosina Quinase
Quinases da Família src
topic Neoplasias / sangue
Mieloma Múltiplo / tratamento farmacológico
Proteínas do Mieloma / análise
ibrutinibe / tratamento farmacológico
Tirosina Quinase
Quinases da Família src
description Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease. The treatments currently available cannot cure the patient, but only extend their lifespan, and the main and most effective alternative is autologous hematopoietic stem cell transplantation, but not every patient is eligible, often due to age and pre-existing comorbidities. In this context, the search for new therapies that can bring better results to patients is of utmost importance. Protein tyrosine kinases (PTKs) are involved in several biological processes, such as cell growth regulation and proliferation, thus, mutations that affect their functionality can have a great impact on crucial molecular pathways in the cells, leading to tumorigenesis. In the past couple of decades, the use of small-molecule inhibitors, which include tyrosine kinase inhibitors (TKIs), has been a hallmark in the treatment of hematological malignancies, and MM patients may also benefit from TKI-based treatment strategies. In this review, we seek to understand the applicability of TKIs used in MM clinical trials in the last 10 years.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-10-03T17:15:48Z
dc.date.available.fl_str_mv 2022-10-03T17:15:48Z
dc.date.issued.fl_str_mv 2022
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dc.identifier.citation.fl_str_mv BARRETO, Igor Valentim et al. Kinase inhibition in multiple myeloma: current scenario and clinical perspectives. Pharmaceutics, v. 14, n. 9, p. 1-16, Aug. 2022. DOI: 10.3390/pharmaceutics14091784. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506264/pdf/pharmaceutics-14-01784.pdf.
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/4669
dc.identifier.issn.-.fl_str_mv 1999-4923
dc.identifier.doi.pt_BR.fl_str_mv 10.3390/pharmaceutics14091784
identifier_str_mv BARRETO, Igor Valentim et al. Kinase inhibition in multiple myeloma: current scenario and clinical perspectives. Pharmaceutics, v. 14, n. 9, p. 1-16, Aug. 2022. DOI: 10.3390/pharmaceutics14091784. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9506264/pdf/pharmaceutics-14-01784.pdf.
1999-4923
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