BCL2L11 and neoplasm: We thus conclude that the cytotoxic activity of biparatopic DARPins, despite being nota bene extracellular ligands, is mainly attributable to activation of the intrinsic apoptotic pathway, and it occurs specifically in ErbB2-addicted tumour cells, as also suggested by the increased expression of the BH3-only pro-apoptotic Bcl-2-like protein 11 (BIM), a master regulator of apoptosis elicited by inhibition of EGFR family receptors35 (Fig. 2g).