Figure 2.

The overview of PI3K/AKT/mTOR, RAS-RAF-MEK-ERK, and MEK5/ERK5 pathway, with their respective small molecule inhibitors. The immune-modulatory effect of both PI3K and MAPK inhibition provides a promising option to overcome therapeutic resistance with ICIs. Dual-targeted inhibition of MAPK and PI3K pathway effectors in combination or with sequential treatment with ICIs may present a potential strategy to overcome resistance in patients with tumors harboring both pathway-associated mutations. FDA-approved therapeutic agents are denoted in red. Inhibitors with an asterisk (*) are approved in melanoma. Created with BioRender.com.