Novel therapeutic targets in Waldenstrom macroglobulinemia

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• 作者：Aneel Paulus^a ; ^{Paulus.aneel@mayo.edu" class="auth_mail" title="E-mail the corresponding author} ; Sikander Ailawadhi^b ; ¹ ; ^{Ailawadhi.sikander@mayo.edu" class="auth_mail" title="E-mail the corresponding author} ; Asher Chanan-Khan^b ; ¹ ; ^{Chanan-Khan.asher@mayo.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Waldenstrom macroglobulinemia ; MYD88 ; Deubiquitinating enzymes ; Ibrutinib ; Proteasome
• 刊名：Best Practice Research Clinical Haematology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：29
• 期：2
• 页码：216-228
• 全文大小：1105 K

文摘

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 MYD88_L265P 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, MYD88_L265P-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.