Table 1 Preclinical trials of ATM-CHK2-p53 alterations and PARPi in cancer cell lines

Prostate

22Rv1 CL1-8

ATM-MUT

ATM-MUT + PARPi + ATRi

(ATM-MUT + Rucaparib + VE-822)

Yes

–

↑

↓

–

No

–

[129]

22Rv1

LNCaP

DU-145

ATM-WT

ATMi + PARPi + ATRi

(Ku-60019 + Rucaparib + VE-822)

Yes

↓(pCHK2 T68 and pCHK1

S345)

↑

↓

–

No

–

Pancreas

AKC

ATM-loss

ATM-loss + PARPi + ATRi + DNA-Pki

(ATM-loss + Olaparib + VE-822 + CC-115)

Yes

–

↑

–

Fork asymmetry;↓

–

↑

[132]

AKC995

ATM-loss

ATM-loss + PARPi ± IR/Gimcitabine

(ATM-loss + olaparib/niraparib + IR/

Gimcitabine);

ATM-loss + ATRi

(ATM-loss + VE-822)

Yes

–

↑

↓

↓

–

↑

[130]

AKC5615

AKC5980

AKC5982

ATM-loss

ATM-loss + PARPi ± IR/Gimcitabine

(ATM-loss + olaparib/niraparib ± IR/

Gimcitabine);

ATM-loss + ATRi

(ATM-loss + VE-822)

Yes

–

(p-CHK1↑

p-KAP1↑)

–

–

–

–

–

[130]

ATM^+/+ MIA PaCa-2

ATM^+/+

ATMi + PARPi + ATRi + DNA-PKi (AZD0156/KU60019 + Olaparib + VE-822 + CC-115)

Yes

–

↑

–

–

–

–

[132]

ATM^+/Δ MIA PaCa-2

ATM^+/Δ

ATM + /Δ + PARPi + ATRi + DNA-Pki

(ATM + /Δ + Olaparib + VE-822 + CC-115)

Yes

–

↑

–

–

–

–

[132]

ATM^Δ/Δ MIA PaCa-2

ATM^Δ/Δ

ATMΔ/Δ + PARPi + ATRi + DNA-PKi

(ATMΔ/Δ + Olaparib + VE-822 + CC-115)

Yes

–

–

–

–

–

–

[132]

Lymph

PGA-shATM

ATM-loss

ATM-loss + PARPi

(ATM-loss + Olaparib)

Yes

–

–

–

–

–

–

[153]

Granta-519

ATM-MUT

ATM-MUT + PARPi

(ATM-MUT + Olaparib)

Yes

–

–

–

–

–

–

[153]

Head and neck

FaDu

ATM-KO

ATM-KO + PARPi + ATRi

(ATM-loss + Olaparib + AZD6738)

Yes

↓

↓(γH2AX↓;micronuclei↑)

–

–

G2/M↓

↑

[154]

Nasopharyngeal

HONE1

ATM-WT

ATMi + PARPi (KU-60019 + Olaparib)

Yes

↑

↑

↓

–

Cell cycle arrest; G2/M↑

–

[155]

ATMi + PARPi

(KU-60019 + Veliparib)

Yes

↑

↑

–

–

G2/M↑

–

[155]

Lung

A549

ATM-KO;

TP53-WT

ATM-KO + PARPi + ATRi

(ATM-KO + Olaparib + AZD6738);

Yes

–

–

–

–

–

↑

[154]

ATM-KO + PARPi

(ATM-KO + Olaparib/Talazoparib)

Yes

↑

↑

–

–

G2↑

↑

[156]

NCI-H2

ATM-MUT

ATM-MUT + PARPi + ATRi

(ATM-MUT + Olaparib + AZD6738

Yes

–

–

↑

[154]

Kidney (Embryo)

HEK293

ATM-WT

ATMi + PARPi

(AZD0156 + Olaparib)

Yes

–

↑

↑

–

–

↑

[157]

Cervix

Hela

p53-deficiency

CHK2i + PARPi

(CCT24153 + Olaparib)

Yes

↓

–

–

–

–

↑

[133]

CHK2i + PARPi

(CCT241533 + Rucaparib)

Yes

–

–

–

–

–

–

[133]

Colon

HT-29

p53-deficiency

CHK2i + PARPi

(CCT241533 + Rucaparib)

Yes

–

–

–

–

–

–

[133]

Breast

MDA-MB468

Mtp53 273H; Mtp53248W

(Gain of function; GOF)

TP53-MUT(GOF) + PARPi + temozolomide

(TP53-MUT(GOF) + Talazoparib + temozolomide)

Ye

–

↓

–

–

–

[137]

MCF-7

TP53-WT

TP53-WT + PARPi + Irradiation

(TP53-WT + Veliparib + Irradiation)

Yes

–

–

–

–

–

–

[139]

MCF-7

Mtp53 273H(GOF)

TP53-MUT(GOF) + PARPi + Irradiation

(TP53-MUT(GOF) + Veliparib + Irradiation)

Yes

–

–

–

–

–

–

[139]

Bladder

UMUC3

TP53-MUT(F113C)

TP53-MUT + PARPi

(TP53-MUT + Olaparib)

Yes

–

↑

No

–

–

–

[138]

5637

TP53-MUT(R280T)

TP53-MUT + PARPi

(TP53-MUT + Olaparib)

Yes

–

No

–

–

–

[138]

639v

TP53-MUT(R248Q)

TP53-MUT + PARPi

(TP53-MUT + Olaparib)

Yes

–

↑

No

–

G1↑

[138]

Colorectum

SKCO1

TP53-WT

TP53-WT + PARPi

(TP53-WT + Talaparib)

Yes

↑

↓

[139]

LS513

TP53-WT

TP53-WT + PARPi

(TP53-WT + Talaparib)

Yes

↑

–

[139]

HCT116

TP53-WT

TP53-WT + PARPi + RMRP-sg-1

(TP53-WT + Olaparib + RMRP-sg-1)

Yes

–

–

–

–

–

[138]

LOVO

TP53-WT

TP53-WT + PARPi + RMRP-sg-1

(TP53-WT + Olaparib + RMRP-sg-1)

Yes

–

–

–

–

–

–

[138]

Cerebrum

U87

TP53-WT

TP53-WT + PARPi + Irradiation

(TP53-WT + Veliparib + Irradiation)

Yes

–

–

↓

–

–

–

[139]

SF767

TP53-WT

TP53-WT + PARPi + Irradiation

(TP53-WT + Veliparib + Irradiation)

Yes

–

–

–

–

–

–

[139]