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Treatment Shows Promise for DLBCL


September 15, 2020

Napabucasin, a novel inhibitor of signal transducer and activator of transcription 3 (STAT3), is a promising candidate for patients with diffuse large B-cell lymphoma (DLBCL), according to paper published online in the journal Cancer Letters. 

“DLBCL, the most common type of aggressive non-Hodgkin lymphoma, has highly heterogeneous molecular characteristics. Although some patients initially respond to standard R–CHOP therapy, 30% to 40% develop refractory disease or suffer relapse,” wrote researchers from Sichuan, China. “STAT3, which regulates multiple oncogenic processes, has been found to be constitutively activated in various cancers, including DLBCL, suggesting its potential as a therapeutic target.” 

Among 69 patients with DLBCL, one third expressed pSTAT3 in tumor tissues, according to the study. In a dose-dependent manner, napabucasin exhibited potent cytotoxicity against non-Hodgkin lymphoma cell lines.  

In mechanistic studies, napabucasin induced intrinsic and extrinsic cell apoptosis, downregulated STAT3 target gene expression, and regulated the reactive oxygen species-mediated mitogen-activated protein kinase pathway.  

“Most importantly,” researchers noted, “in vivo studies revealed the suppressive efficacy of napabucasin as a monotherapy without obvious toxicity.” 

In preliminary investigations, researchers added, napabucasin showed significant synergism with doxorubicin in vitro as well as in vivo. 

Jolynn Tumolo 

Reference

Li X, Wei Y, Wei X. Napabucasin, a novel inhibitor of STAT3, inhibits growth and synergises with doxorubicin in diffuse large B-cell lymphoma [published online ahead of print, 2020 Aug 14]. Cancer Lett. 2020;491:146-161. doi:10.1016/j.canlet.2020.07.032

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