Diffuse Large B Cell Lymphoma (Dlbcl) Expresses Ror1 And A Ror1 Small Molecule Inhibitor (Kan0441571c) Induced Significant Apoptosis Of Tumor Cells

BLOOD(2019)

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摘要
Background: Receptor tyrosine kinase (RTK) (ROR1) is normally expressed during embryogenesis but absent in most normal tissues. However, ROR1 is overexpressed in several cancers (onco-fetal RTK) and of importance for various tumor cell functions such as proliferation and survival. In patients with diffuse large B-cell lymphomas (DLBCL) there is a great medical need to develop new treatment alternatives for those not responding to primary treatment as well as for patients with relapse as effective treatments are warranted. Inhibition of ROR1 by a small molecule ROR1 inhibitor (KAN0439834) abrogated downstream kinase activities as well as induced apoptosis of various tumor cells as CLL and pancreatic carcinoma (Leukemia, Oct;32(10):2291-2295, 2018) (PLoS One. 13(6): e0198038, 2018). A 2nd generation of ROR1 inhibitor (KAN0441571C) has been synthesized with the aim to bind to the ROR1-TK domain and inhibit ROR1 signaling.
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