The inhibition of the alternative NFĸB pathway and BCL-2 targeting as a potential therapeutic approach for the treatment of classical Hodgkin Lymphoma

DIAZ M; SANCHEZ CARO S; MASCARDI MF; DELGADO PASTORE M; VALEFF NJ; PETERS MG; TRINKS J; PENAS STEINHARDT A; RANUNCOLO SM

Congreso; LXVI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2021

Sociedad Argentina de Investigación Clínica (SAIC)

Refractory/relapsed (R/R) disease in classical Hodgkin Lymphoma (cHL) is the major challenge making necessary the development of new therapeutic strategies. We have previously reported that the non-canonical NFĸB pathway (NCP) plays a key role in human cHL cells survival, being NIK stabilization responsible for its constitutive signaling. Also, we have shown that BCL-2 sustained expression is partially a consequence of this mechanism and should be considered as a prognosis biomarker. The aim of this work was to explore the mechanism underlying the anti-tumor effects of the NCP and BCL-2 inhibition after treatment with 4H-isoquinoline-1,3-dione (iNIK) and venetoclax (VTX), respectively, or their combination in human cHL cell lines from R/R patients. Trypan blue exclusion and MTS assays showed that treatment with iNIK decreased cell growth in all cell lines (p