TY - JOUR
T1 - Novel therapeutic targets in Waldenstrom macroglobulinemia
AU - Paulus, Aneel
AU - Ailawadhi, Sikander
AU - Chanan-Khan, Asher
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Understanding of molecular mechanisms that drive Waldenstrom macroglobulinemia (WM) cell survival are rapidly evolving. This review briefly highlights emerging “WM-relevant” targets; for which therapeutic strategies are currently being investigated in preclinical and clinical studies. With the discovery of MYD88L265P signaling and remarkable activity of ibrutinib in WM, other targets within the B-cell receptor pathway are now being focused on for therapeutic intervention. Additional targets which play a role in WM cell survival include TLR7, 8 and 9, proteasome-associated deubiquitinating enzymes (USP14 and UCHL5), XPO1/CRM1 and AURKA. New drugs for established targets are also discussed. Lastly, we spotlight 3 highly innovative WM-specific therapies: MYD88 peptide inhibitors, MYD88L265P-directed immune activation and CD19-directed chimeric antigen receptor T-cell therapy, which are in various stages of development. Indeed, treatment of WM is poised to undergo a paradigm shift in the coming years towards highly disease-driven and more personalized therapeutic modalities with curative intent.
AB - Understanding of molecular mechanisms that drive Waldenstrom macroglobulinemia (WM) cell survival are rapidly evolving. This review briefly highlights emerging “WM-relevant” targets; for which therapeutic strategies are currently being investigated in preclinical and clinical studies. With the discovery of MYD88L265P signaling and remarkable activity of ibrutinib in WM, other targets within the B-cell receptor pathway are now being focused on for therapeutic intervention. Additional targets which play a role in WM cell survival include TLR7, 8 and 9, proteasome-associated deubiquitinating enzymes (USP14 and UCHL5), XPO1/CRM1 and AURKA. New drugs for established targets are also discussed. Lastly, we spotlight 3 highly innovative WM-specific therapies: MYD88 peptide inhibitors, MYD88L265P-directed immune activation and CD19-directed chimeric antigen receptor T-cell therapy, which are in various stages of development. Indeed, treatment of WM is poised to undergo a paradigm shift in the coming years towards highly disease-driven and more personalized therapeutic modalities with curative intent.
KW - Deubiquitinating enzymes
KW - Ibrutinib
KW - MYD88
KW - Proteasome
KW - Waldenstrom macroglobulinemia
UR - http://www.scopus.com/inward/record.url?scp=84994514643&partnerID=8YFLogxK
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U2 - 10.1016/j.beha.2016.08.020
DO - 10.1016/j.beha.2016.08.020
M3 - Review article
C2 - 27825468
AN - SCOPUS:84994514643
SN - 1521-6926
VL - 29
SP - 216
EP - 228
JO - Best Practice and Research: Clinical Haematology
JF - Best Practice and Research: Clinical Haematology
IS - 2
ER -