STAT3 inhibition is a therapeutic strategy for ABC-like diffuse large B-cell lymphoma

Authors

Anna Scuto, City of Hope National Med Center
Maciej Kujawski, City of Hope National Med Center
Claudia Kowolik, City of Hope National Med Center
Ludmila Krymskaya, City of Hope National Med Center
Lin Wang, City of Hope National Med Center
Lawrence M. Weiss, City of Hope National Med Center
David DiGiusto, City of Hope National Med Center
Hua Yu, City of Hope National Med Center
Stephen Forman, City of Hope National Med Center
Richard Jove, City of Hope National Med Center

Abstract

Persistent STAT3 signaling contributes to malignant progression in many diverse types of human cancer. STAT3 is constitutively active in activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL), a class of nongerminal center derived DLBCL cells for which existing therapy is weakly effective. In this report, we provide a preclinical proof of concept that STAT3 is an effective molecular target for ABC-like DLBCL therapy. Direct inhibition of STAT3 with short hairpin RNA suppressed the growth of human ABC-like DLBCL in mouse models in a manner associated with apoptosis, repression of STAT3 target genes, and inhibition of a tumor-promoting microenvironment. Together, these results suggest that STAT3 is essential to maintain the pathophysiology of ABC-like DLBCL and therefore that STAT3 inhibition may offer a promising approach in its therapy. ©2011 AACR.

Publication Title

Cancer Research

Recommended Citation

Scuto, A., Kujawski, M., Kowolik, C., Krymskaya, L., Wang, L., Weiss, L., DiGiusto, D., Yu, H., Forman, S., & Jove, R. (2011). STAT3 inhibition is a therapeutic strategy for ABC-like diffuse large B-cell lymphoma. Cancer Research, 71 (9), 3182-3188. https://doi.org/10.1158/0008-5472.CAN-10-2380