Fig. 8: Proposed model for how targeted activation of GPER improves the antileukemic activity of venetoclax.

G-1 and VEN synergistically trigger simultaneous apoptosis and GSDME-dependent pyroptosis via activating the p38-MAPK/MCL-1 axis in leukemic cells. Moreover, the release of IL-1β/18 induced by pyroptosis heightens the tumor suppressive function of CD8+ T cells.