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Table 3 Preclinical studies evaluating the effect of WEE1 inhibitors in monotherapy or in combination with chemotherapy/radiotherapy in cancer

From: A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target

Inhibitor Treatment Cancer model Main biological effect References
PD0166285 M GBM-astrocytoma -G2/M checkpoint override
-Forced mitotic entry
[51]
Adavosertib M MM, ALL, AML TNBC, DLBCL, MCL -G2/M checkpoint override
-Forced mitotic entry
-Mitotic catastrophe
-Replicative catastrophe
[35, 99, 119,120,121,122]
PD0166285 +R GBM-astrocytoma -Mitotic catastrophe
-Inhibition of DNA repair
[51]
Adavosertib +R CC, LC, BC, PC, OC, DLBCL, ES -Increased DNA damage
-Induction of apoptosis
-Mitotic catastrophe
[78, 99, 123,124,125,126]
Adavosertib +C AML, ALL, MM, BC, CC, GC, DLBCL -S or G2/M checkpoint override
-Increased DNA damaged
-Induction of apoptosis
[35, 37, 38, 76, 92, 99, 121, 127,128,129]
Adavosertib +HDAC i AML, HNSCC -Replication stress
-Replicative catastrophe
-Increased DNA damage
-Inhibition of DNA repair
[41, 130, 131]
Adavosertib +ATR i AML, DLBCL, MCL, BC -Replication stress
-Replicative catastrophe
-Increased DNA damaged
-Inhibition of DNA repair
[132,133,134,135]
Adavosertib +mTOR i AML, ALL, OC, NSCLC -Inhibition of DNA repair [136,137,138,139]
Adavosertib +CHK1 i MCL, DLBCL, ALL, AML -Replication stress
-Increased DNA damage
-Replicative catastrophe
[103, 140,141,142]
Adavosertib +BCL2i/MCL-1 i DLBCL -Force mitotic entry
-Increase DNA damage
-INDUCTION of apoptosis
[143]
Adavosertib +PARP1 i NSCLC, AML, ALL -G2/M checkpoint override
-Replication stress
-Increased DNA damage
-Inhibition of DNA repair
[126, 144,145,146]
Adavosertib +AURORA A i HNSCC -Forced mitotic entry
-Mitotic catastrophe
[147]
Adavosertib +CDK2 i BC -Replication stress
-Replicative catastrophe
[89]
Adavosertib +SIRT1 i LC -Inhibition of DNA repair [148]
Adavosertib +CDK4-6 i S -Replication stress [149]
Adavosertib +BCR-ABL1 i ALL -Inhibition of DNA repair -G2/M checkpoint override [35]
Adavosertib +Proteasome i MM -G2/M checkpoint override
-Forced mitotic entry
-Inhibition of DNA repair
[36]
Adavosertib +BET i NSCLC -Inhibition of DNA repair
-Forced mitotic entry
-Mitotic catastrophe
[150]
  1. M monotherapy, R radiotherapy, C chemotherapy, ALL acute lymphoblastic leukemia, AML acute myeloid leukemia, MM multiple myeloma, DLBCL diffuse large B cell lymphoma, MCL mantle cell lymphoma, GC gastric cancer, GL gliomas, OC ovarian cancer, CC colorectal cancer, PC pancreatic cancer, ES esophageal cancer, HC hepatocellular carcinoma, GLB glioblastoma, NSCLC non-small-cell lung cancer, N neuroblastoma, S sarcomas, LC lung cancer, BC breast cancer, HNSCC head and neck squamous cell carcinoma, TNBC triple negative breast cancer