Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance

Detalhes bibliográficos
Autor(a) principal: Alves, Raquel
Data de Publicação: 2021
Outros Autores: Gonçalves, Ana Cristina, Rutella, Sergio, Almeida, António M., Rivas, Javier De Las, Trougakos, Ioannis P., Ribeiro, Ana Bela Sarmento
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.14/35386
Resumo: Resistance to targeted therapies is a complex and multifactorial process that culminates in the selection of a cancer clone with the ability to evade treatment. Chronic myeloid leukemia (CML) was the first malignancy recognized to be associated with a genetic alteration, the t(9;22)(q34;q11). This translocation originates the BCR-ABL1 fusion gene, encoding the cytoplasmic chimeric BCR-ABL1 protein that displays an abnormally high tyrosine kinase activity. Although the vast majority of patients with CML respond to Imatinib, a tyrosine kinase inhibitor (TKI), resistance might occur either de novo or during treatment. In CML, the TKI resistance mechanisms are usually subdivided into BCR-ABL1-dependent and independent mechanisms. Furthermore, patients’ compliance/adherence to therapy is critical to CML management. Techniques with enhanced sensitivity like NGS and dPCR, the use of artificial intelligence (AI) techniques, and the development of mathematical modeling and computational prediction methods could reveal the underlying mechanisms of drug resistance and facilitate the design of more effective treatment strategies for improving drug efficacy in CML patients. Here we review the molecular mechanisms and other factors involved in resistance to TKIs in CML and the new methodologies to access these mechanisms, and the therapeutic approaches to circumvent TKI resistance.
id RCAP_f79e5cc541fab53b7ba30a1e606337ec
oai_identifier_str oai:repositorio.ucp.pt:10400.14/35386
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevanceBioinformatics and artificial intelligenceCMLEpigeneticsImmune systemNew targeted therapiesPatient adherenceTKI resistanceResistance to targeted therapies is a complex and multifactorial process that culminates in the selection of a cancer clone with the ability to evade treatment. Chronic myeloid leukemia (CML) was the first malignancy recognized to be associated with a genetic alteration, the t(9;22)(q34;q11). This translocation originates the BCR-ABL1 fusion gene, encoding the cytoplasmic chimeric BCR-ABL1 protein that displays an abnormally high tyrosine kinase activity. Although the vast majority of patients with CML respond to Imatinib, a tyrosine kinase inhibitor (TKI), resistance might occur either de novo or during treatment. In CML, the TKI resistance mechanisms are usually subdivided into BCR-ABL1-dependent and independent mechanisms. Furthermore, patients’ compliance/adherence to therapy is critical to CML management. Techniques with enhanced sensitivity like NGS and dPCR, the use of artificial intelligence (AI) techniques, and the development of mathematical modeling and computational prediction methods could reveal the underlying mechanisms of drug resistance and facilitate the design of more effective treatment strategies for improving drug efficacy in CML patients. Here we review the molecular mechanisms and other factors involved in resistance to TKIs in CML and the new methodologies to access these mechanisms, and the therapeutic approaches to circumvent TKI resistance.Veritati - Repositório Institucional da Universidade Católica PortuguesaAlves, RaquelGonçalves, Ana CristinaRutella, SergioAlmeida, António M.Rivas, Javier De LasTrougakos, Ioannis P.Ribeiro, Ana Bela Sarmento2021-10-04T15:20:46Z2021-10-012021-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.14/35386eng2072-669410.3390/cancers1319482085115641235PMC850837834638304000707334800001info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-12T01:34:37Zoai:repositorio.ucp.pt:10400.14/35386Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:28:44.048681Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance
title Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance
spellingShingle Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance
Alves, Raquel
Bioinformatics and artificial intelligence
CML
Epigenetics
Immune system
New targeted therapies
Patient adherence
TKI resistance
title_short Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance
title_full Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance
title_fullStr Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance
title_full_unstemmed Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance
title_sort Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from molecular mechanisms to clinical relevance
author Alves, Raquel
author_facet Alves, Raquel
Gonçalves, Ana Cristina
Rutella, Sergio
Almeida, António M.
Rivas, Javier De Las
Trougakos, Ioannis P.
Ribeiro, Ana Bela Sarmento
author_role author
author2 Gonçalves, Ana Cristina
Rutella, Sergio
Almeida, António M.
Rivas, Javier De Las
Trougakos, Ioannis P.
Ribeiro, Ana Bela Sarmento
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Veritati - Repositório Institucional da Universidade Católica Portuguesa
dc.contributor.author.fl_str_mv Alves, Raquel
Gonçalves, Ana Cristina
Rutella, Sergio
Almeida, António M.
Rivas, Javier De Las
Trougakos, Ioannis P.
Ribeiro, Ana Bela Sarmento
dc.subject.por.fl_str_mv Bioinformatics and artificial intelligence
CML
Epigenetics
Immune system
New targeted therapies
Patient adherence
TKI resistance
topic Bioinformatics and artificial intelligence
CML
Epigenetics
Immune system
New targeted therapies
Patient adherence
TKI resistance
description Resistance to targeted therapies is a complex and multifactorial process that culminates in the selection of a cancer clone with the ability to evade treatment. Chronic myeloid leukemia (CML) was the first malignancy recognized to be associated with a genetic alteration, the t(9;22)(q34;q11). This translocation originates the BCR-ABL1 fusion gene, encoding the cytoplasmic chimeric BCR-ABL1 protein that displays an abnormally high tyrosine kinase activity. Although the vast majority of patients with CML respond to Imatinib, a tyrosine kinase inhibitor (TKI), resistance might occur either de novo or during treatment. In CML, the TKI resistance mechanisms are usually subdivided into BCR-ABL1-dependent and independent mechanisms. Furthermore, patients’ compliance/adherence to therapy is critical to CML management. Techniques with enhanced sensitivity like NGS and dPCR, the use of artificial intelligence (AI) techniques, and the development of mathematical modeling and computational prediction methods could reveal the underlying mechanisms of drug resistance and facilitate the design of more effective treatment strategies for improving drug efficacy in CML patients. Here we review the molecular mechanisms and other factors involved in resistance to TKIs in CML and the new methodologies to access these mechanisms, and the therapeutic approaches to circumvent TKI resistance.
publishDate 2021
dc.date.none.fl_str_mv 2021-10-04T15:20:46Z
2021-10-01
2021-10-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.14/35386
url http://hdl.handle.net/10400.14/35386
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2072-6694
10.3390/cancers13194820
85115641235
PMC8508378
34638304
000707334800001
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799132006578126848