Table 2 Preclinical trials of PARPi and ATR-CHK1-WEE1 inhibitors in cancer cell lines

Ovary

Acquired PR

PEO1-PR

BRCA2-MUT

ATRi + PARPi

(AZD6738 + Olaparib)

Yes

↑

↑

↓

↓

No

↑

[125]

JHOS4-PR

BRCA1-MUT

ATRi + PARPi

(AZD6738 + Olaparib)

Yes

↑

↑

No

↓

No

↑

[125]

UWB1.289 SYR1

BRCA1-MUT

ATRi + PARPi

(VE-821 + Olaparib)

Ye

–

–

↓

↓

–

[124]

UWB1.289 SYR12*

BRCA1-MUT

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

–

–

–

–

[86]

UWB1.289 SYR13

BRCA1-MUT

ATRi + PARPi

(VE-821 + Olaparib)

Yes

–

–

↓

–

–

[124]

UWB1.289 SYR1

BRCA1-MUT

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

–

–

–

–

–

–

[86]

BR5-R1

BRCA1-MU

ATRi + PARPi

(VE-821 + Olaparib)

Yes

–

–

–

–

[124]

De novo PR

UWB1.289/BRCA1 ± 

BRCA1 ± 

ATRi + PARPi

(VE-821 + Olaparib)

No

–

–

↓

No

–

–

[124]

ATRi + PARPi

(AZD6738 + Olaparib)

Yes

↑

↑

↓

–

No

–

[125]

UWB1.289/53BP1−/−

BRCA1-MUT

ATRi + PARPi

(AZD6738 + Olaparib)

Ye

–

–

–

–

No

–

[125]

COV362/53BP1−/−

BRCA1-MUT

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

–

–

↓

–

–

–

[86]

Kuramochi

BRCA2-nonse mutation (c.6952C > T)

ATRi + PARPi

(AZD6738 + Olaparib)

Yes

↑

↑

No

–

No

–

[125]

PEO4

BRCA2-reversion mutation

ATRi + PARPi

(AZD6738 + Olaparib)

Yes

↓

–

–

–

G2/M↑

↑

[141]

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

pATR↑/pCHK1↓

↑

↓

–

G2/M↓

↑

[143]

Preexisting PR

OV-9

TP53-MUT

BRCA-WT

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

pATR↑/pCHK1↓

↑

↓

–

–

↑

[143]

ATRi + PARPi

(AZD6738 + Olaparib

Yes

↑

↑

–

–

–

↑

[123]

CHK1i + PARPi

(MK8776 + Olaparib)

Yes

↑

↑

–

–

–

[123]

SKOV3

BRCA-WT

ATRi + PARPi + siBRCA1

(VE-821 + Velaparib + 

siBRCA1)

Yes

–

–

↓

–

–

–

[158]

ATRi + PARPi

(AZD6738 + Olaparib)

Yes

–

↑

–

–

–

↑

[123]

CHK1i + PARPi

(MK8776 + Olaparib)

Yes

–

↑

–

–

–

↑

[123]

TOV112D

BRCA1-WT

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

–

–

–

–

–

–

[86]

ES2

BRCA1-WT

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

–

–

–

–

–

–

[86]

OVCAR-8

BRCA-WT

ATRi + PARPi + siBRCA1

(VE-821 + Velaparib + 

siBRCA1)

Yes

–

–

–

–

–

[158]

OVCAR3

BRCA wild type;

TP53-MUT(R248Q)

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

pATR↑/Pchk1↓

↑

↓

–

G2/M↓

↑

[143]

WEE1i + PARPi

(AZD1775 + Olaparib)

Yes

–

–

–

–

M↑

↑

[159]

PARPi-sensitive

PEO1

BRCA2-MUT(c.C4965G)

ATRi + PARPi

(AZD6738 + Olaparib)

Yes

↓

↑

–

–

G2/M↓

↑

[141]

ATRi + PARPi

(VE-821 + Velaparib)

Yes

–

–

–

–

–

–

[158]

CHK1i + PARPi

(MK8776 + Olaparib

Yes

↓

↑

–

–

G2/M↓

↑

[141]

[123]

CHK1i + PARPi

(Prexasertib + Olaparib)

Yes

pATR↑/Pchk1↓

↑

↓

–

G2/M↓

↑

[143]

–

EM9

XRCC1−/−

ATRi + PARPi

(NU6027 + Rucaparib)

Yes

–

–

–

–

–

–

[160]

Breast

Preexisting PR

HCC1937

BRCA1-deficient

ATRi + PARPi

(VE-821 + Velaparib)

Yes

–

–

↓

–

–

–

[124]

–

MCF7

–

ATRi + PARPi

(NU6027 + Rucaparib)

Yes

–

↑

↓

–

–

–

[160]

Pancreas

Acquired PR

R-AKC

ATM-MUT

ATRi + PARPi + DNA-PKi + P-gpi

(VE-822 + Olaparib + CC-115 + Elacridar)

Yes

–

–

–

–

G2/M↑

–

[132]

Lung

De novo PR

VC8-B2

BRCA2 + / + 

ATRi + PARPi

(NU6027 + Rucaparib)

Yes

–

–

↓

–

–

–

[160]

CHK1i + PARPi

(PF-47736 + Rucaparib)

Yes

↓

↑

↓

–

S↓G2/M↓ sub-G1↑

–

[144]

Endometrium

Preexisting PR

Hec50

BRCA-WT;TP53-MUT(intron 6)

BRCA-WT;TP53-MUT(intron 6)

Yes

–

–

–

–

M↑

↑

[159]

Gastric

–

MKN45

–

WEE1i + PARPi

(AZD1775 + Olaparib)

Yes

–

↑

↓

–

G2/M↓

↑

[146]

–

AGS

–

WEE1i + PARPi

(AZD1775 + Olaparib)

Yes

–

↑

↓

–

G2/M↓

↑

[146]

Brain

–

MGG18

Non MYC-MUT

ATRi + PARPi

(VE-822 + Olaparib)

Yes

↑

↑

↓

–

–

↑

[161]