Systematic identification of synthetic lethal interactions that operate in cancer

Reviews on this subject

Synthetic lethal therapies for cancer: what's next after PARP inhibitors?
Ashworth A, Lord CJ. Nat Rev Clin Oncol. 2018 Jun 28.

Genetic interactions in cancer progression and treatment.
Ashworth A, Lord CJ, Reis-Filho JS.
Cell. 2011 Apr 1;145(1):30-8.

Tankyrase-targeted therapeutics: expanding opportunities in the PARP family.
Riffell JL, Lord CJ, Ashworth A.
Nat Rev Drug Discov. 2012 Dec;11(12):923-36.

Rethinking ovarian cancer: recommendations for improving outcomes.
Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR.
Nat Rev Cancer. 2011 Sep 23;11(10):719-25.

Searching for synthetic lethality in cancer.
Brough R, Frankum JR, Costa-Cabral S, Lord CJ, Ashworth A.
Curr Opin Genet Dev. 2011 Feb;21(1):34-41.

Synthetic lethal approaches to breast cancer therapy.
Rehman FL, Lord CJ, Ashworth A.
Nat Rev Clin Oncol. 2010 Dec;7(12):718-24.

Biology-driven cancer drug development: back to the future.
Lord CJ, Ashworth A.
BMC Biol. 2010 Apr 12;8:38.

Utilizing RNA interference to enhance cancer drug discovery.
Iorns E, Lord CJ, Turner N, Ashworth A.
Nat Rev Drug Discov. 2007 Jul;6(7):556-68.

Selected research papers on this subject

E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.
Bajrami I, Marlow R, van de Ven M, Brough R, Pemberton HN, Frankum J, Song F, Rafiq R, Konde A, Krastev DB, Menon M, Campbell J, Gulati A, Kumar R, Pettitt SJ, Gurden MD, Cardenosa ML, Chong I, Gazinska P, Wallberg F, Sawyer EJ, Martin LA, Dowsett M, Linardopoulos S, Natrajan R, Ryan CJ, Derksen PWB, Jonkers J, Tutt ANJ, Ashworth A, Lord CJ. Cancer Discov. 2018 Apr;8(4):498-515. 

Identification of highly penetrant Rb-related synthetic lethal interactions in triple negative breast cancer. Brough R, Gulati A, Haider S, Kumar R, Campbell J, Knudsen E, Pettitt SJ, Ryan CJ, Lord CJ. Oncogene. 2018 Jun 18.

Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer. Witkiewicz AK, Chung S, Brough R, Vail P, Franco J, Lord CJ, Knudsen ES. Cell Rep. 2018 Jan 30;22(5):1185-1199. 

ATR Is a Therapeutic Target in Synovial Sarcoma. Jones SE, Fleuren EDG, Frankum J, Konde A, Williamson CT, Krastev DB, Pemberton HN, Campbell J, Gulati A, Elliott R, Menon M, Selfe JL, Brough R, Pettitt SJ, Niedzwiedz W, van der Graaf WTA, Shipley J, Ashworth A, Lord CJ. Cancer Res. 2017 Dec 15;77(24):7014-7026

A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events. Ryan CJ, Kennedy S, Bajrami I, Matallanas D, Lord CJ. Cell Syst. 2017 Oct 25;5(4):399-409.e5.

The genomic landscape of oesophagogastric junctional adenocarcinoma.
Chong IY, Cunningham D, Barber LJ, Campbell J, Chen L, Kozarewa I, Fenwick K, Assiotis I, Guettler S, Garcia-Murillas I, Awan S, Lambros M, Starling N, Wotherspoon A, Stamp G, Gonzalez-de-Castro D, Benson M, Chau I, Hulkki S, Nohadani M, Eltahir Z, Lemnrau A, Orr N, Rao S, Lord CJ, Ashworth A.
J Pathol. 2013 Nov;231(3):301-10.

Identification of novel determinants of resistance to lapatinib in ERBB2-amplified cancers.
Wetterskog D, Shiu KK, Chong I, Meijer T, Mackay A, Lambros M, Cunningham D, Reis-Filho JS, Lord CJ, Ashworth A. Oncogene. 2014 Feb 20;33(8):966-76. 

Integrative molecular and functional profiling of ERBB2-amplified breast cancers identifies new genetic dependencies.
Shiu KK, Wetterskog D, Mackay A, Natrajan R, Lambros M, Sims D, Bajrami I, Brough R, Frankum J, Sharpe R, Marchio C, Horlings H, Reyal F, van der Vijver M, Turner N, Reis-Filho JS, Lord CJ, Ashworth A.
Oncogene. 2014 Jan 30;33(5):619-31.

Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer.
Ruark E, Snape K, Humburg P, Loveday C, Bajrami I, Brough R, Rodrigues DN, Renwick A, Seal S, Ramsay E, Duarte Sdel V, Rivas MA, Warren-Perry M, Zachariou A, Campion-Flora A, Hanks S, Murray A, Ansari Pour N, Douglas J, Gregory L, Rimmer A, Walker NM, Yang TP, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Eccles D, Evans DG, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, Gore M, Houlston R, Brown MA, Caufield MJ, Deloukas P, McCarthy MI, Todd JA; Breast and Ovarian Cancer Susceptibility Collaboration; Wellcome Trust Case Control Consortium, Turnbull C, Reis-Filho JS, Ashworth A, Antoniou AC, Lord CJ, Donnelly P, Rahman N.
Nature. 2013 Jan 17;493(7432):406-10

NLK is a novel therapeutic target for PTEN deficient tumour cells.
Mendes-Pereira AM, Lord CJ, Ashworth A.
PLoS One. 2012;7(10):e47249.

High-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing.
Sims D, Mendes-Pereira AM, Frankum J, Burgess D, Cerone MA, Lombardelli C, Mitsopoulos C, Hakas J, Murugaesu N, Isacke CM, Fenwick K, Assiotis I, Kozarewa I, Zvelebil M, Ashworth A, Lord CJ.
Genome Biol. 2011 Oct 21;12(10):R104.

Functional viability profiles of breast cancer.
Brough R, Frankum JR, Sims D, Mackay A, Mendes-Pereira AM, Bajrami I, Costa-Cabral S, Rafiq R, Ahmad AS, Cerone MA, Natrajan R, Sharpe R, Shiu KK, Wetterskog D, Dedes KJ, Lambros MB, Rawjee T, Linardopoulos S, Reis-Filho JS, Turner NC, Lord CJ, Ashworth A.
Cancer Discov. 2011 Aug;1(3):260-73.

High-throughput RNAi screening reveals novel regulators of telomerase.
Cerone MA, Burgess DJ, Naceur-Lombardelli C, Lord CJ, Ashworth A.
Cancer Res. 2011 May 1;71(9):3328-40.

Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen.
Mendes-Pereira AM, Sims D, Dexter T, Fenwick K, Assiotis I, Kozarewa I, Mitsopoulos C, Hakas J, Zvelebil M, Lord CJ, Ashworth A.
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2730-5.

Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer.
McCabe N, Cerone MA, Ohishi T, Seimiya H, Lord CJ, Ashworth A.
Oncogene. 2009 Mar 19;28(11):1465-70.

Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer.
Iorns E, Turner NC, Elliott R, Syed N, Garrone O, Gasco M, Tutt AN, Crook T, Lord CJ, Ashworth A.
Cancer Cell. 2008 Feb;13(2):91-104.