Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and accounts for the majority of aggressive non-Hodgkin lymphoma cases in the US. While it is a curable disease with significant success from rituximab and CHOP chemotherapeutic treatment, a significant minority of patients with advanced stage disease and clinical risk factors are in need of alternative treatment strategies.
Scientists at NCI’s Lymphoid Malignancies Branch, have developed a novel stapled-peptide that specifically targets the linear polyubiquitin chain assembly complex (LUBAC), a pathway involved in NF-κB activation via binding of two protein molecules, RNF31 and RBCK1. The investigators have genetic, biochemical and functional evidence showing that the These cell-permeable peptides compete against endogenous RNF31, therefore inhibit the NF-kB induction pathway and kill the malignant cells.
- Targeted therapies for ABC DLBCL.
- Combination cytotoxic chemotherapies for ABC DLBCL.
- Treatment for other cancers or autoimmune/inflammatory diseases that depend upon the function of RNF31 and RBCK1 combination.
- Novel composition of inhibitors for advance stage ABC DLBCL, Effective therapies targeting at NF-kB pathway, Novel therapeutic for ABC DLBCL not responsive to rituximab and CHOP chemotherapy.
Yang Y et al. Essential role of the linear ubiquitin chain assembly complex in lymphoma revealed by rare germline polymorphisms. [PMID: 24491438]
- U.S. Patent Filed: U.S. Patent Application Number 61/789,064, Filed 15 Mar 2013