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Patient-derived xenograft models of ALK+ ALCL reveal preclinical promise for therapy with brigatinib

Prokoph, Nina ; Matthews, Jamie D ; Trigg, Ricky M ; Montes-Mojarro, Ivonne A ; Burke, G A Amos ; Fend, Falko ; Merkel, Olaf ; Kenner, Lukas ; Geoerger, Birgit ; Johnston, Robert ; Murray, Matthew J ; Riguad, Charlotte ; Brugières, Laurence ; Turner, Suzanne D

British journal of haematology, 2023-09, Vol.202 (5), p.985-994 [Periódico revisado por pares]

England: Blackwell Publishing Ltd

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Título:
Patient-derived xenograft models of ALK+ ALCL reveal preclinical promise for therapy with brigatinib
Autor: Prokoph, Nina ; Matthews, Jamie D ; Trigg, Ricky M ; Montes-Mojarro, Ivonne A ; Burke, G A Amos ; Fend, Falko ; Merkel, Olaf ; Kenner, Lukas ; Geoerger, Birgit ; Johnston, Robert ; Murray, Matthew J ; Riguad, Charlotte ; Brugières, Laurence ; Turner, Suzanne D
Assuntos: Anaplastic Lymphoma Kinase ; Blood-brain barrier ; Carcinoma, Non-Small-Cell Lung ; Central nervous system ; Chemotherapy ; Child ; Crizotinib - pharmacology ; Crizotinib - therapeutic use ; Hematology ; Heterografts ; Hodgkin's lymphoma ; Humans ; Lung cancer ; Lung Neoplasms - drug therapy ; Lymphoma ; Lymphoma, Large-Cell, Anaplastic - drug therapy ; Lymphoma, Large-Cell, Anaplastic - pathology ; Malignancy ; Neoplasm Recurrence, Local - drug therapy ; Organophosphorus Compounds - pharmacology ; Organophosphorus Compounds - therapeutic use ; Original Paper ; p53 Protein ; Paediatrics ; Pediatrics ; Protein Kinase Inhibitors - therapeutic use ; Protein-tyrosine kinase ; Receptor Protein-Tyrosine Kinases - therapeutic use ; Remission ; Xenografts
É parte de: British journal of haematology, 2023-09, Vol.202 (5), p.985-994
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Nina Prokoph and Jamie D. Matthews contributed equally to this work.
Descrição: Anaplastic large-cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by the oncogenic anaplastic lymphoma kinase (ALK), accounting for approximately 15% of all paediatric non-Hodgkin lymphoma. Patients with central nervous system (CNS) relapse are particularly difficult to treat with a 3-year overall survival of 49% and a median survival of 23.5 months. The second-generation ALK inhibitor brigatinib shows superior penetration of the blood-brain barrier unlike the first-generation drug crizotinib and has shown promising results in ALK+ non-small-cell lung cancer. However, the benefits of brigatinib in treating aggressive paediatric ALK+ ALCL are largely unknown. We established a patient-derived xenograft (PDX) resource from ALK+ ALCL patients at or before CNS relapse serving as models to facilitate the development of future therapies. We show in vivo that brigatinib is effective in inducing the remission of PDX models of crizotinib-resistant (ALK C1156Y, TP53 loss) ALCL and furthermore that it is superior to crizotinib as a second-line approach to the treatment of a standard chemotherapy relapsed/refractory ALCL PDX pointing to brigatinib as a future therapeutic option.
Editor: England: Blackwell Publishing Ltd
Idioma: Inglês

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Patient-derived xenograft models of ALK+ ALCL reveal preclinical promise for therapy with brigatinib

Prokoph, Nina ; Matthews, Jamie D ; Trigg, Ricky M ; Montes-Mojarro, Ivonne A ; Burke, G A Amos ; Fend, Falko ; Merkel, Olaf ; Kenner, Lukas ; Geoerger, Birgit ; Johnston, Robert ; Murray, Matthew J ; Riguad, Charlotte ; Brugières, Laurence ; Turner, Suzanne D

England: Blackwell Publishing Ltd

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