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

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]