FIGURE 2.

GNAQ or GNA11 mutations cause the constitutive activation of Gα, which activates signaling by activating phospholipase C (PLCβ) and protein kinase C (PKC). The activation of the RAS-dependent RAF pathway leads to the formation of the RAS-GTP–Raf-1 complex, inducing the activation of the downstream ERK1/2 pathway and the mitogen-activated protein kinase (MAPK) pathway. PKC inhibitors, such as sotrastuarin and darovasertib, inhibit the conventional PKC isoform, PKCβ, PKC, and the novel PKC isoforms, PKC δ and PKCε, thus suppressing the downstream signaling cascade, which decreases tumor cell proliferation and survival (Wei et al., 2022). Reproduced with permission from ref. (Wei et al., 2022). Copyright 2022, Springer Nature.