Hence, GPER is also implicated in obesity and DM.188 In terms of the roles of tamoxifen and GPER in PC, recent studies suggest that through the activation of GPER, tamoxifen reduces fibrosis and desmoplastic tissues by targeting PSCs and ameliorates the infiltration of macrophages by lowering the stiffness of the ECM while mitigating hypoxia and angiogenesis in the TME, which promotes apoptosis, inhibits cell proliferation, and prevents cancer progression189,190 (Fig. 4). Here, GPER1 is linked to obesity due to melanocortin 4 receptor deficiency.