Lysosome-mediated chemoresistance in acute myeloid leukemia
Cuesta-Casanovas, Laia (Universitat Autònoma de Barcelona)
Delgado-Martínez, Jennifer (Universitat de Barcelona)
Cornet-Masana, Josep Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Carbó, José María (Leukos Biotech)
Clément-Demange, Lise (Leukos Biotech (Barcelona))
Risueño, Ruth M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Date:	2022
Abstract:	Despite the outstanding advances in understanding the biology underlying the pathophysiology of acute myeloid leukemia (AML) and the promising preclinical data published lastly, AML treatment still relies on a classic chemotherapy regimen largely unchanged for the past five decades. Recently, new drugs have been approved for AML, but the real clinical benefit is still under evaluation. Nevertheless, primary refractory and relapse AML continue to represent the main clinical challenge, as the majority of AML patients will succumb to the disease despite achieving a complete remission during the induction phase. As such, treatments for chemoresistant AML represent an unmet need in this disease. Although great efforts have been made to decipher the biological basis for leukemogenesis, the mechanism by which AML cells become resistant to chemotherapy is largely unknown. The identification of the signaling pathways involved in resistance may lead to new combinatory therapies or new therapeutic approaches suitable for this subset of patients. Several mechanisms of chemoresistance have been identified, including drug transporters, key secondary messengers, and metabolic regulators. However, no therapeutic approach targeting chemoresistance has succeeded in clinical trials, especially due to broad secondary effects in healthy cells. Recent research has highlighted the importance of lysosomes in this phenomenon. Lysosomes' key role in resistance to chemotherapy includes the potential to sequester drugs, central metabolic signaling role, and gene expression regulation. These results provide further evidence to support the development of new therapeutic approaches that target lysosomes in AML.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Cancer Drug Resistance, Vol. 5 Núm. 1 (2022) , p. 233-244, ISSN 2578-532X

DOI: 10.20517/cdr.2021.122
PMID: 35582535

12 p, 752.8 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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