Kinase inhibition in multiple myeloma: current scenario and clinical perspectives
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , |
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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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 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
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 10.3390/pharmaceutics14091784 |
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https://patua.iec.gov.br/handle/iec/4669 |
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