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

DÏAZ, MARIÁNGELES; SANCEHZ-CARO, SOFÍA; MASCARDI, MARÍA FLORENCIA; DELGADO PASTORE, MAGALÍ; VALEFF, NATALIA JIMENA; PETERS, MARÍA GISELLE; TRINKS, JULIETA; PENAS STEINHARDT, ALBERTO; RANUNCOLO, STELLA MARIS

Buenos Aires

Congreso; Reunión conjunta de SAIC, SAI, AAFE y NANOMED.AR; 2021

SOciedad Argentina de Investigación CLínica (SAIC)

Refractory/relapsed (R/R) disease in classical Hodgkin Lymphoma (cHL) is the major challengemaking necessary the development of new therapeutic strategies. We have previously reportedthat 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 thatBCL-2 sustained expression is partially a consequence of this mechanism and should beconsidered as a prognosis biomarker. The aim of this work was to explore the mechanismunderlying 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 inhuman cHL cell lines from R/R patients. Trypan blue exclusion and MTS assays showed thattreatment with iNIK decreased cell growth in all cell lines (p