MAPK3 and non-small cell lung carcinoma: Coincidentally, in non-small cell lung cancer (NSCLC) the downstream kinases of EGFR, such as Akt, ERK1/2, will phosphorylate ERα that binds to estradiol at the Ser118 site, thereby enhancing its transcriptional activity and upregulating the expression of PD-L1 (Figure 2B) (64).