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Table 1 Genetic alterations that predict PARPi sensitivity

From: Use of poly ADP-ribose polymerase [PARP] inhibitors in cancer cells bearing DDR defects: the rationale for their inclusion in the clinic

Altered gene PARP inhibitors in vitro/in vivo systems Study
BRCA2 NU1025 and AG14361 Chinese hamster cell
V-C8 and V-C8 + B2
(BRCA2 defective and BRCA2 complemented)
Human breast cancer cells
MCF-7 or MDA-MB-231
(BRCA2 siRNA)
Bryant H. et al., Nature 2005.
.
KU0058684 and KU0058948 Mouse ESC
(lacking BRCA2 wt)
HeLa
(RNAi)
Farmer H. et al, Nature 2005
McCabe N. et al., Cancer Res. 2006
Olaparib (AZD2281) Ovarian cancer patients ClinicalTrial NCT00753545
Prostate cancer patients
ClinicalTrial, NCT01682772
Ledermann J. et al., N Engl J Med. 2012.
Mateo J. et al., N. Engl. J. Med. 2015.
ATM KU0058684 and KU0058948
Olaparib (AZD2281)
HeLa
(RNAi)
Prostate cancer patients
ClinicalTrial, NCT01682772
McCabe N. et al., Cancer Res. 2006.
Mateo J. et al., N. Engl. J. Med. 2015.
ATR KU0058684 and KU0058948 HeLa
(RNAi)
McCabe N. et al., Cancer Res. 2006
FANC A/F KU0058684 and KU0058948
Olaparib (AZD2281)
Mouse fibroblast
(FANC KO)
Prostate cancer patients
ClinicalTrial, NCT01682772
McCabe N. et al., Cancer Res. 2006
Mateo J. et al., N. Engl. J. Med. 2015.
CHK2 KU0058684 and KU0058948
Olaparib (AZD2281)
HeLa
(RNAi)
Prostate cancer patients
ClinicalTrial, NCT01682772
McCabe N. et al., Cancer Res. 2006
Mateo J. et al., N. Engl. J. Med. 2015.).
BRCA1 KU0058684 and KU0058948
Olaparib (AZD2281)
Mouse ESC
(lacking BRCA2 wt)
HeLa
(RNAi)
Ovarian cancer patients ClinicalTrial NCT00753545
Prostate cancer patients
ClinicalTrial, NCT01682772
Farmer H. et al, Nature. 2005.
McCabe N. et al., Cancer Res. 2006.
Ledermann J. et al., N Engl J Med. 2012.
Mateo J. et al., N. Engl. J. Med. 2015.
PALB2 Olaparib (AZD2281)
BMN 673
Human fibroblast EUFA1341
(express PALB2 mutant)
Wilms tumor KT-10 cells
(express truncated PALB2)
Buisson R. etal., Nat Struct Mol Biol. 2010.
Smith MA. et al., Pediatr Blood Cancer. 2015.
RAD51B/C KU0058684 and KU0058948
Olaparib (AZD2281)
HeLa
(RNAi)
Prostate cancer patients
ClinicalTrial, NCT01682772
McCabe N. et al., Cancer Res. 2006.
Mateo J. et al., N. Engl. J. Med. 2015.
RAD54 KU0058684 and KU0058948 Mouse ESC
(lacking Rad54 wt)
McCabe N. et al., Cancer Res. 2006.
ERCC1 olaparib
(AZD-2281), niraparib
(MK-4827),
BMN 673
olaparib
(AZD-2281),
veliparib
(ABT-888)
Non Small Cell Lung Cancer
A549
(ERCC1 deficient clones)
Non Small Cell Lung Cancer
HCC827, PC9
(ERCC1 low expression)
Postel-Vinay S. et al., Oncogene 2013.
Cheng H. et al., Carcinogenesis 2013.
CtIP BMN 673
KU0058948
Myeloid leukemia cell K562 (expressing CtIP-T) Gaymes TJ. et al., Haematologica. 2013.
MRE11 BMN 673
KU0058948
Hystiocitic Linphoma U937 cell
(expressing MRE11-Δ57)
Gaymes TJ. et al., Haematologica. 2013.
NBS1 KU0058684 and KU0058948 Human immortalized fibroblast McCabe N. et al., Cancer Res. 2006.
DSS1 KU0058684 and KU0058948 HeLa
(RNAi)
McCabe N. et al., Cancer Res. 2006.
RPA1 KU0058684 and KU0058948 HeLa
(RNAi)
McCabe N. et al., Cancer Res. 2006.
PTEN (KU0059436) Olaparib Colorectal tumour cell
HCT116 (truncated PTEN) endometroid adenocarcinoma cells HEC1A (truncated PTEN)
Breast, prostate, melanoma, glioma and bladder cells
HCC70, MDA-MB-468, PC3, RPMI-7951, A172, UM-UC3 and (PTEN deficient expression)
Mendes-Pereira, A. et al., EMBO Mol. Med. 2009.
(KU0059436) Olaparib Prostate cancer patients ClinicalTrial, NCT01682772 Mateo J. et al., N. Engl. J. Med. 2015.
ETS/ERG (KU0059436) Olaparib
MK-4827
Solid tumors ClinicalTrial, NCT00777582
Solid tumors ClinicalTrial, NCT00749502
Brenner JC. et al, Cancer Res. 2011.
XRCC2/XRCC3 (3-AB)
(ISQ)
(NU1025) (AG14361)
Chinese hamster ovary cell irs1/irs1SF Bryant H. et al., Nature 2005.
CDK1 AG14361 and
AG014699
Non Small Cell Lung Cancer
NCI-H1299/A549
CDK1 (RNAi)
Johnson N. et al., Nat Med. 2011.
CDK12 veliparib
(ABT-888)
Ovarian cancer
OVCAR-3, OVCAR-5, OVCAR-8
CDK12 (RNAi)
Joshi, P.M. et al., J. Biol. Chem. 2014.
Bajrami,I. . et al., Cancer Res. 2014.
olaparib
(AZD-2281)
Ovarian cancer
PEO1, OV56, COV504;
OV90 cells
CDK12-(RNAi)
 
(KU0059436) Olaparib Prostate cancer patients ClinicalTrial, NCT01682772 Mateo J. et al., N. Engl. J. Med. 2015.
CDK5 KU0058948 Breast cancer
CAL51 cells
CDK5 (RNAi)
Turner, N.C. et al., EMBO J. 2008.
PLK3 KU0058948 Breast cancer
CAL51 cells
PLK3 (RNAi)
Turner, N.C. et al., EMBO J. 2008.
PNKP KU0058948 Breast cancer
CAL51 cells
PNKP (RNAi)
Turner, N.C. et al., EMBO J. 2008.
STK22C KU0058948 Breast cancer
CAL51 cells
STK22C (RNAi)
Turner, N.C. et al., EMBO J. 2008.
STK36 KU0058948 Breast cancer
CAL51 cells
STK36 (RNAi)
Turner, N.C. et al., EMBO J. 2008.
USP1 KU0058948 Breast cancer
CAL51 cells
USP1 (RNAi)
Turner, N.C. et al., EMBO J. 2008.
USP11 olaparib
(AZD-2281)
Bone osteosarcoma
U2OS cell
USP11 (RNAi)
Wiltshire TD. et al., J Biol Chem. 2010.
CCDC6 olaparib
(AZD-2281),
Non Small Cell Lung Cancer
H1975 cells
CCDC6 (RNAi)
Morra F. et al., Int J Cancer 2015.