From: Targeting mutant p53 for cancer therapy: direct and indirect strategies
Synthetic lethal partner | Mechanism | References |
---|---|---|
ATR | ATR inhibitors target ATR/CHK1 pathway to suppress G2 arrest in p53-deficient cancers | |
CHK1 | CHK1 inhibitors target CHK1 to suppress G2 arrest in p53-deficient cancers | [70] |
p38MAPK/MK2 | MK2 regulates of G2/M and S-phase checkpoint in p53-mutated/p53-deficient cancers in response to DNA damage | |
WEE1 | WEE1 plays a crucial role in the G2/M transition for p53-mutated cancers | |
PLK1 | PLK1 is required for mitosis entry by activating CDC25 and inhibiting both WEE1 and PKMYT1 | |
PIP4K2B | High level of PI5P4Ks promotes glucose uptake to support glucose metabolism and enhances NADPH generation to mediated ROS response in the condition of p53 mutation/deletion | [89] |
HK2 | HK2 regulates the transform from phosphorylating glucose into glucose-6-phosphate to elevate glycolysis for glycolysis | |
mTOR | mTOR-induced inhibition of autophagy prevents mutp53 proteins from autophagy-mediated degradation | [96] |
PDGFRβ | PDGFRβ maintains the premetastatic phenotype for pancreatic ductal adenocarcinoma with p53 R172H | [103] |
PLA2G16 | Mutp53 binds to the promoter of PLA2G16 to promote metastatic phenotype | [104] |