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Optimising the clinical use of PARP inhibitors


Reviews on this subject

PARP inhibitors: Synthetic lethality in the clinic.
Lord CJ, Ashworth A. 

Science. 2017 Mar 17;355(6330):1152-1158

Mechanisms of resistance to therapies targeting BRCA-mutant cancers.
Lord CJ, Ashworth A.

Nat Med. 2013 Nov;19(11):1381-8.

The potential of exploiting DNA-repair defects for optimizing lung cancer treatment.
Postel-Vinay S, Vanhecke E, Olaussen KA, Lord CJ, Ashworth A, Soria JC.
Nat Rev Clin Oncol. 2012 Feb 14;9(3):144-55.

The DNA damage response and cancer therapy.
Lord CJ, Ashworth A.
Nature. 2012 Jan 18;481(7381):287-94.

Targeted therapy for cancer using PARP inhibitors.
Lord CJ, Ashworth A.
Curr Opin Pharmacol. 2008 Aug;8(4):363-9.

Targeting the double-strand DNA break repair pathway as a therapeutic strategy.
Lord CJ, Garrett MD, Ashworth A.
Clin Cancer Res. 2006 Aug 1;12(15):4463-8.

Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer.
Tutt AN, Lord CJ, McCabe N, Farmer H, Turner N, Martin NM, Jackson SP, Smith GC, Ashworth A.
Cold Spring Harb Symp Quant Biol. 2005;70:139-48.


Original research papers on this subject

The shieldin complex mediates 53BP1-dependent DNA repair. Noordermeer SM, Adam S, Setiaputra D, Barazas M, Pettitt SJ, Ling AK, Olivieri M, Álvarez-Quilón A, Moatti N, Zimmermann M, Annunziato S, Krastev DB, Song F, Brandsma I, Frankum J, Brough R, Sherker A, Landry S, Szilard RK, Munro MM, McEwan A, Goullet de Rugy T, Lin ZY, Hart T, Moffat J, Gingras AC, Martin A, van Attikum H, Jonkers J, Lord CJ, Rottenberg S, Durocher D. Nature. 2018 Aug;560(7716):117-121

Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets. Krastev DB, Pettitt SJ, Campbell J, Song F, Tanos BE, Stoynov SS, Ashworth A, Lord CJ. Nat Commun. 2018 May 22;9(1):2016.

Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. Pettitt SJ, Krastev DB, Brandsma I, Dréan A, Song F, Aleksandrov R, Harrell MI, Menon M, Brough R, Campbell J, Frankum J, Ranes M, Pemberton HN, Rafiq R, Fenwick K, Swain A, Guettler S, Lee JM, Swisher EM, Stoynov S, Yusa K, Ashworth A, Lord CJ. Nat Commun. 2018 May 10;9(1):1849. 

Modeling Therapy Resistance in BRCA1/2-Mutant Cancers. Dréan A, Williamson CT, Brough R, Brandsma I, Menon M, Konde A, Garcia-Murillas I, Pemberton HN, Frankum J, Rafiq R, Badham N, Campbell J, Gulati A, Turner NC, Pettitt SJ, Ashworth A, Lord CJ. Mol Cancer Ther. 2017 Sep;16(9):2022-2034.

Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition. Goodall J, Mateo J, Yuan W, Mossop H, Porta N, Miranda S, Perez-Lopez R, Dolling D, Robinson DR, Sandhu S, Fowler G, Ebbs B, Flohr P, Seed G, Rodrigues DN, Boysen G, Bertan C, Atkin M, Clarke M, Crespo M, Figueiredo I, Riisnaes R, Sumanasuriya S, Rescigno P, Zafeiriou Z, Sharp A, Tunariu N, Bianchini D, Gillman A, Lord CJ, Hall E, Chinnaiyan AM, Carreira S, de Bono JS; TOPARP-A investigators. Cancer Discov. 2017 Sep;7(9):1006-1017.

Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity.
Bajrami I, Frankum JR, Konde A, Miller RE, Rehman FL, Brough R, Campbell J, Sims D, Rafiq R, Hooper S, Chen L, Kozarewa I, Assiotis I, Fenwick K, Natrajan R, Lord CJ, Ashworth A.
Cancer Res. 2014 Jan 1;74(1):287-97. 

BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency.
Shen Y, Rehman FL, Feng Y, Boshuizen J, Bajrami I, Elliott R, Wang B, Lord CJ, Post LE, Ashworth A.
Clin Cancer Res. 2013 Sep 15;19(18):5003-15.

A high-throughput screen identifies PARP1/2 inhibitors as a potential therapy for ERCC1-deficient non-small cell lung cancer.
Postel-Vinay S, Bajrami I, Friboulet L, Elliott R, Fontebasso Y, Dorvault N, Olaussen KA, André F, Soria JC, Lord CJ, Ashworth A. Oncogene. 2013 Nov 21;32(47):5377-87.
Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study.
Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, De Greve J, Atkinson T, Yap TA, Sandhu S, Banerjee S, Chen LM, Friedlander ML, Kaufman B, Oza AM, Matulonis U, Barber LJ, Kozarewa I, Fenwick K, Assiotis I, Campbell J, Chen L, de Bono JS, Gore ME, Lord CJ, Ashworth A, Kaye SB. Clin Cancer Res. 2013 Oct 1;19(19):5485-93. 

A genetic screen using the PiggyBac transposon in haploid cells identifies Parp1 as a mediator of olaparib toxicity.
Pettitt SJ, Rehman FL, Bajrami I, Brough R, Wallberg F, Kozarewa I, Fenwick K, Assiotis I, Chen L, Campbell J, Lord CJ, Ashworth A. PLoS One. 2013 Apr 25;8(4):e61520. 

Identification of miRNA modulators to PARP inhibitor response.
Neijenhuis S, Bajrami I, Miller R, Lord CJ, Ashworth A. DNA Repair (Amst). 2013 Jun 1;12(6):394-402.

Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor.
Barber LJ, Sandhu S, Chen L, Campbell J, Kozarewa I, Fenwick K, Assiotis I, Rodrigues DN, Reis Filho JS, Moreno V, Mateo J, Molife LR, De Bono J, Kaye S, Lord CJ, Ashworth A.
J Pathol. 2013 Feb;229(3):422-9.

Synthetic lethality of PARP and NAMPT inhibition in triple-negative breast cancer cells.
Bajrami I, Kigozi A, Van Weverwijk A, Brough R, Frankum J, Lord CJ, Ashworth A.
EMBO Mol Med. 2012 Oct;4(10):1087-96.

APRIN is a cell cycle specific BRCA2-interacting protein required for genome integrity and a predictor of outcome after chemotherapy in breast cancer.
Brough R, Bajrami I, Vatcheva R, Natrajan R, Reis-Filho JS, Lord CJ, Ashworth A.
EMBO J. 2012 Mar 7;31(5):1160-76.

Germline mutations in RAD51D confer susceptibility to ovarian cancer.
Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, Bowden G, Kalmyrzaev B, Warren-Perry M, Snape K, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L; Breast Cancer Susceptibility Collaboration (UK), Eccles D, Evans DG, Renwick A, Seal S, Lord CJ, Ashworth A, Reis-Filho JS, Antoniou AC, Rahman N.
Nat Genet. 2011 Aug 7;43(9):879-82. 

PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors.
Dedes KJ, Wetterskog D, Mendes-Pereira AM, Natrajan R, Lambros MB, Geyer FC, Vatcheva R, Savage K, Mackay A, Lord CJ, Ashworth A, Reis-Filho JS.
Sci Transl Med. 2010 Oct 13;2(53):53ra75. 

Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors.
Mendes-Pereira AM, Martin SA, Brough R, McCarthy A, Taylor JR, Kim JS, Waldman T, Lord CJ, Ashworth A. EMBO Mol Med. 2009 Sep;1(6-7):315-22.

A high-throughput RNA interference screen for DNA repair determinants of PARP inhibitor sensitivity.
Lord CJ, McDonald S, Swift S, Turner NC, Ashworth A.
DNA Repair (Amst). 2008 Dec 1;7(12):2010-9. 

A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor.
Turner NC, Lord CJ, Iorns E, Brough R, Swift S, Elliott R, Rayter S, Tutt AN, Ashworth A.
EMBO J. 2008 May 7;27(9):1368-77.

Resistance to therapy caused by intragenic deletion in BRCA2.
Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, Boyd J, Reis-Filho JS, Ashworth A.
Nature. 2008 Feb 28;451(7182):1111-5. 

Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition.
McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, Giavara S, O'Connor MJ, Tutt AN, Zdzienicka MZ, Smith GC, Ashworth A.
Cancer Res. 2006 Aug 15;66(16):8109-15.

BRCA2-deficient CAPAN-1 cells are extremely sensitive to the inhibition of Poly (ADP-Ribose) polymerase: an issue of potency.
McCabe N, Lord CJ, Tutt AN, Martin NM, Smith GC, Ashworth A.
Cancer Biol Ther. 2005 Sep;4(9):934-6.

Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.
Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A.
Nature. 2005 Apr 14;434(7035):917-21.