Researchers at the University of Cologne have identified a new molecular target for the treatment of diffuse large B-cell lymphoma (DLBCL). The protein cFLIP plays a central role in defending against programmed cell death in these cancer cells. The study was conducted under the direction of Dr. Alessandro Annibaldi at the Center for Molecular Medicine Cologne (CMMC) and published in the journal Blood .

The team showed that DLBCL cells – especially the aggressive ABC subtype – strongly overproduce cFLIP in addition to BCL2. As a result, they block both the intrinsic and extrinsic apoptosis pathways and become resistant to conventional therapies. Frontline immunochemotherapy with rituximab cures about 60 percent of patients, but about half suffer relapses or do not respond to treatment.

By specifically inhibiting cFLIP, the Cologne scientists were able to lift the apoptosis blockade and reactivate cell death in the lymphoma cells. In preclinical models, this prevented tumor development. Doctoral student Kristie Bariboloka, who led the experimental work, emphasized the clinical relevance of this approach.

The results lay the foundation for the development of cFLIP-specific inhibitors that could be used alone or in combination with existing drugs – regardless of further mutations in the tumor cells. The researchers see this as a promising option for patients who do not respond to standard therapies.

The work was carried out as part of the Collaborative Research Centre 1530 “Elucidation and Targeting of Pathogenic Mechanisms in B-Cell Neoplasms”, funded by the German Research Foundation (DFG).

Original Paper:

Expression of cFLIP in B cells is essential for diffuse large B-cell lymphoma pathogenesis – PubMed

Editor: X-Press Journalistenbüro GbR

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