Table 1 Genetic alterations that predict PARPi sensitivity

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.