Fig. 5
From: The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy
Combinatorial targeting of hyperactive Ras/RAF/MEK/ERK (MAPK) signaling and AMPK-mediated autophagy to treat Ras/RAF-mutated cancers. Blocking hyperactive Ras/RAF/MEK/ERK (MAPK) signaling by MAPK inhibitors in Ras/RAF-mutated cancer cells elevates autophagic flux through relieving LKB1/AMPK/ULK1 axis and inhibiting glycolysis and mitochondrial functions, which leads to drug tolerance and/or acquired resistance. Combinatorial inhibition of both hyperactive MAPK signaling and autophagy remarkably improves therapeutic efficacy of drugs against these cancers