A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells

ROR1 – a receptor tyrosine kinase – is overexpressed in CLL. Ibrutinib, a Bruton's tyrosine kinase inhibitor, is clinically effective in CLL but patients may develop resistance. We evaluated the effect of an ROR1 inhibitor, KAN0441571C, in CLL cells from six patients obtained before and after d...

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Detalles Bibliográficos
Autores principales: Ghaderi, Amineh, Okhovat, Mohammad‐Ali, Wikanthi, Layung Sekar Sih, Svensson, Ann, Palma, Marzia, Schultz, Johan, Olin, Thomas, Österborg, Anders, Mellstedt, Håkan, Hojjat‐Farsangi, Mohammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Short Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176142/
https://www.ncbi.nlm.nih.gov/pubmed/35844694
http://dx.doi.org/10.1002/jha2.232
Descripción
Sumario:ROR1 – a receptor tyrosine kinase – is overexpressed in CLL. Ibrutinib, a Bruton's tyrosine kinase inhibitor, is clinically effective in CLL but patients may develop resistance. We evaluated the effect of an ROR1 inhibitor, KAN0441571C, in CLL cells from six patients obtained before and after developing resistance to ibrutinib. The ROR1 inhibitor induced apoptosis in ibrutinib‐resistant CLL cells to the same degree as in ibrutinib‐sensitive cells and dephosphorylated ROR1. This was also noted in one patient who became resistant to both ibrutinib and the Bcl‐2 inhibitor venetoclax. The combination of ROR1 inhibitor and venetoclax had a synergistic apoptotic effect on ibrutinib‐resistant cells.

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