Fig. 8: A working model shows the molecular mechanism underlying the ability of the dopamine receptor D2 (DRD2) antagonist penfluridol to retard growth of clear cell renal cell carcinoma (ccRCC) cells.

The anticancer activity of penfluridol on ccRCC cells was attributed to induction of ER stress leading to UPR-mediated autophagy and subsequently induction of apoptosis. Meanwhile, penfluridol not only triggers apoptosis but also attenuates stemness of ccRCC cells via inhibiting Akt/GLI1/OCT4/Nanog axis. Bold dashed lines indicate hypothetical pathways which might be inhibited by penfluridol.