Recent submissions

  • Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors. 

    Yap, TA; O'Carrigan, B; Penney, MS; Lim, JS; Brown, JS; de Miguel Luken, MJ; Tunariu, N; Perez-Lopez, R; Rodrigues, DN; Riisnaes, R; Figueiredo, I; Carreira, S; Hare, B; McDermott, K; Khalique, S; Williamson, CT; Natrajan, R; Pettitt, SJ; Lord, CJ; Banerji, U; Pollard, J; Lopez, J; de Bono, JS (2020-06-22)
    PURPOSE:Preclinical studies demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired compensatory DNA damage responses through ATM loss) as monotherapy and combined with DNA-damaging ...
  • ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor positive breast cancer: A combined analysis of the phase III SoFEA and EFECT trials. 

    Turner, NC; Swift, C; Kilburn, LS; Fribbens, C; Beaney, M; Garcia-Murillas, I; Buzdar, AU; Roberston, JF; Gradishar, W; Piccart, M; Schiavon, G; Bliss, JM; Dowsett, M; Johnston, SRD; Chia, SK (2020-06-16)
    PURPOSE:ESR1 mutations are acquired frequently in hormone receptor positive (HR+) metastatic breast cancer after prior aromatase inhibitors (AI). We assessed the clinical utility of baseline ESR1 circulating tumor DNA ...
  • Prognostic Value of EndoPredict in Women with Hormone Receptor Positive, HER2-Negative Invasive Lobular Breast Cancer. 

    Sestak, I; Filipits, M; Buus, R; Rudas, M; Balic, M; Knauer, M; Kronenwett, R; Fitzal, F; Cuzick, J; Gnant, M; Greil, R; Dowsett, M; Dubsky, P (2020-06-19)
    PURPOSE:Invasive lobular carcinoma (ILC) accounts for approximately 5-15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients ...
  • Evidence-based guidelines for managing patients with primary ER+ HER2- breast cancer deferred from surgery due to the COVID-19 pandemic. 

    Dowsett, M; Ellis, MJ; Dixon, JM; Gluz, O; Robertson, J; Kates, R; Suman, VJ; Turnbull, AK; Nitz, U; Christgen, M; Kreipe, H; Kuemmel, S; Bliss, JM; Barry, P; Johnston, SR; Jacobs, SA; Ma, CX; Smith, IE; Harbeck, N (2020-01)
    Many patients with ER+ HER2- primary breast cancer are being deferred from surgery to neoadjuvant endocrine therapy (NeoET) during the COVID-19 pandemic. We have collated data from multiple international trials of presurgical ...
  • Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology-Genomic Integration Analysis. 

    Natrajan, R; Sailem, H; Mardakheh, FK; Arias Garcia, M; Tape, CJ; Dowsett, M; Bakal, C; Yuan, Y (2016-02-16)
    The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess ...
  • Phase I trial of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib and AKT inhibitor capivasertib in patients with BRCA1/2 and non-BRCA1/2 mutant cancers. 

    Yap, TA; Kristeleit, R; Michalarea, V; Pettitt, SJ; Lim, JSJ; Carreira, S; Roda, D; Miller, R; Riisnaes, R; Miranda, S; Figueiredo, I; Nava Rodrigues, D; Ward, S; Matthews, R; Parmar, M; Turner, A; Tunariu, N; Chopra, N; Gevensleben, H; Turner, NC; Ruddle, R; Raynaud, FI; Decordova, SA; Swales, KE; Finneran, L; Hall, E; Rugman, P; Lindemann, JPO; Foxley, A; Lord, CJ; Banerji, U; Plummer, R; Basu, B; Lopez, JS; Drew, Y; de Bono, JS (2020-06-12)
    Preclinical studies have demonstrated synergy between poly(ADP-ribose) polymerase (PARP) and phosphatidylinositol-3-kinase (PI3K)/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. ...
  • Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer. 

    Chopra, N; Tovey, H; Pearson, A; Cutts, R; Toms, C; Proszek, P; Hubank, M; Dowsett, M; Dodson, A; Daley, F; Kriplani, D; Gevensleben, H; Davies, HR; Degasperi, A; Roylance, R; Chan, S; Tutt, A; Skene, A; Evans, A; Bliss, JM; Nik-Zainal, S; Turner, NC (2020-05-29)
    Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO ...
  • Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth. 

    Lechertier, T; Reynolds, LE; Kim, H; Pedrosa, AR; Gómez-Escudero, J; Muñoz-Félix, JM; Batista, S; Dukinfield, M; Demircioglu, F; Wong, PP; Matchett, KP; Henderson, NC; D'Amico, G; Parsons, M; Harwood, C; Meier, P; Hodivala-Dilke, KM (2020-06-04)
    The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is ...
  • PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer. 

    Chabanon, RM; Muirhead, G; Krastev, DB; Adam, J; Morel, D; Garrido, M; Lamb, A; Hénon, C; Dorvault, N; Rouanne, M; Marlow, R; Bajrami, I; Cardeñosa, ML; Konde, A; Besse, B; Ashworth, A; Pettitt, SJ; Haider, S; Marabelle, A; Tutt, AN; Soria, J-C; Lord, CJ; Postel-Vinay, S (2019-03)
    The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA ...
  • Evaluation of Cancer-Based Criteria for Use in Mainstream BRCA1 and BRCA2 Genetic Testing in Patients With Breast Cancer. 

    Kemp, Z; Turnbull, A; Yost, S; Seal, S; Mahamdallie, S; Poyastro-Pearson, E; Warren-Perry, M; Eccleston, A; Tan, M-M; Teo, SH; Turner, N; Strydom, A; George, A; Rahman, N (2019-05-03)
    Importance:Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers. Objective:To evaluate mainstream genetic testing using ...
  • Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation. 

    Dalton, WB; Helmenstine, E; Walsh, N; Gondek, LP; Kelkar, DS; Read, A; Natrajan, R; Christenson, ES; Roman, B; Das, S; Zhao, L; Leone, RD; Shinn, D; Groginski, T; Madugundu, AK; Patil, A; Zabransky, DJ; Medford, A; Lee, J; Cole, AJ; Rosen, M; Thakar, M; Ambinder, A; Donaldson, J; DeZern, AE; Cravero, K; Chu, D; Madero-Marroquin, R; Pandey, A; Hurley, PJ; Lauring, J; Park, BH (2019-08-08)
    Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are ...
  • Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival. 

    Tonnessen-Murray, CA; Frey, WD; Rao, SG; Shahbandi, A; Ungerleider, NA; Olayiwola, JO; Murray, LB; Vinson, BT; Chrisey, DB; Lord, CJ; Jackson, JG (2019-11)
    In chemotherapy-treated breast cancer, wild-type p53 preferentially induces senescence over apoptosis, resulting in a persisting cell population constituting residual disease that drives relapse and poor patient survival ...
  • Longitudinal analysis of a secondary BRCA2 mutation using digital droplet PCR. 

    Khalique, S; Pettitt, SJ; Kelly, G; Tunariu, N; Natrajan, R; Banerjee, S; Lord, CJ (2020-01)
    Development of resistance to platinum and poly(ADP-ribose) polymerase inhibitors via secondary BRCA gene mutations that restore functional homologous recombination has been observed in a number of cancer types. Here we ...
  • Translational genomics of ovarian clear cell carcinoma. 

    Khalique, S; Lord, CJ; Banerjee, S; Natrajan, R (2019-11-04)
    Ovarian clear cell carcinomas (OCCC) are rare aggressive, chemo-resistant tumours comprising approximately 13% of all epithelial ovarian cancers, which have distinct clinical and molecular features, when compared to other ...
  • Next Generation Sequencing Assay for Detection of Circulating HPV DNA (cHPV-DNA) in Patients Undergoing Radical (Chemo)Radiotherapy in Anal Squamous Cell Carcinoma (ASCC). 

    Lee, JY; Cutts, RJ; White, I; Augustin, Y; Garcia-Murillas, I; Fenwick, K; Matthews, N; Turner, NC; Harrington, K; Gilbert, DC; Bhide, S (2020-01)
    Background: Following chemo-radiotherapy (CRT) for human papilloma virus positive (HPV+) anal squamous cell carcinoma (ASCC), detection of residual/recurrent disease is challenging. Patients frequently undergo unnecessary ...
  • Quizartinib-resistant FLT3-ITD acute myeloid leukemia cells are sensitive to the FLT3-Aurora kinase inhibitor CCT241736. 

    Moore, AS; Faisal, A; Mak, GWY; Miraki-Moud, F; Bavetsias, V; Valenti, M; Box, G; Hallsworth, A; de Haven Brandon, A; Xavier, CPR; Stronge, R; Pearson, ADJ; Blagg, J; Raynaud, FI; Chopra, R; Eccles, SA; Taussig, DC; Linardopoulos, S (2020-04)
    Internal tandem duplication of FLT3 (FLT3-ITD) is one of the most common somatic mutations in acute myeloid leukemia (AML); it causes constitutive activation of FLT3 kinase and is associated with high relapse rates and ...
  • Genetic Alterations in the PI3K/AKT Pathway and Baseline AKT Activity Define AKT Inhibitor Sensitivity in Breast Cancer Patient-derived Xenografts. 

    Gris-Oliver, A; Palafox, M; Monserrat, L; Brasó-Maristany, F; Òdena, A; Sánchez-Guixé, M; Ibrahim, YH; Villacampa, G; Grueso, J; Parés, M; Guzmán, M; Rodríguez, O; Bruna, A; Hirst, CS; Barnicle, A; de Bruin, EC; Reddy, A; Schiavon, G; Arribas, J; Mills, GB; Caldas, C; Dienstmann, R; Prat, A; Nuciforo, P; Razavi, P; Scaltriti, M; Turner, NC; Saura, C; Davies, BR; Oliveira, M; Serra, V (2020-03-27)
    PURPOSE:AZD5363/capivasertib is a pan-AKT catalytic inhibitor with promising activity in combination with paclitaxel in triple-negative metastatic breast cancer harboring PI3K/AKT-pathway alterations and in estrogen ...
  • The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche. 

    Ataca, D; Aouad, P; Constantin, C; Laszlo, C; Beleut, M; Shamseddin, M; Rajaram, RD; Jeitziner, R; Mead, TJ; Caikovski, M; Bucher, P; Ambrosini, G; Apte, SS; Brisken, C (2020-03-26)
    Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. How they control the extracellular matrix, important ...
  • RIPK1-mediated immunogenic cell death promotes anti-tumour immunity against soft-tissue sarcoma. 

    Smith, HG; Jamal, K; Dayal, JH; Tenev, T; Kyula-Currie, J; Guppy, N; Gazinska, P; Roulstone, V; Liccardi, G; Davies, E; Roxanis, I; Melcher, AA; Hayes, AJ; Inman, GJ; Harrington, KJ; Meier, P (2020-06)
    Drugs that mobilise the immune system against cancer are dramatically improving care for many people. Dying cancer cells play an active role in inducing anti-tumour immunity but not every form of death can elicit an immune ...
  • Combined associations of a polygenic risk score and classical risk factors with breast cancer risk. 

    Kapoor, PM; Mavaddat, N; Choudhury, PP; Wilcox, AN; Lindström, S; Behrens, S; Michailidou, K; Dennis, J; Bolla, MK; Wang, Q; Jung, A; Abu-Ful, Z; Ahearn, T; Andrulis, IL; Anton-Culver, H; Arndt, V; Aronson, KJ; Auer, PL; Freeman, LEB; Becher, H; Beckmann, MW; Beeghly-Fadiel, A; Benitez, J; Bernstein, L; Bojesen, SE; Brauch, H; Brenner, H; Brüning, T; Cai, Q; Campa, D; Canzian, F; Carracedo, A; Carter, BD; Castelao, JE; Chanock, SJ; Chatterjee, N; Chenevix-Trench, G; Clarke, CL; Couch, FJ; Cox, A; Cross, SS; Czene, K; Dai, JY; Earp, HS; Ekici, AB; Eliassen, AH; Eriksson, M; Evans, DG; Fasching, PA; Figueroa, J; Fritschi, L; Gabrielson, M; Gago-Dominguez, M; Gao, C; Gapstur, SM; Gaudet, MM; Giles, GG; González-Neira, A; Guénel, P; Haeberle, L; Haiman, CA; Håkansson, N; Hall, P; Hamann, U; Hatse, S; Heyworth, J; Holleczek, B; Hoover, RN; Hopper, JL; Howell, A; Hunter, DJ; ABCTB Investigators; kConFab/AOCS Investigators; John, EM; Jones, ME; Kaaks, R; Keeman, R; Kitahara, CM; Ko, Y-D; Koutros, S; Kurian, AW; Lambrechts, D; Marchand, LL; Lee, E; Lejbkowicz, F; Linet, M; Lissowska, J; Llaneza, A; MacInnis, RJ; Martinez, ME; Maurer, T; McLean, C; Neuhausen, SL; Newman, WG; Norman, A; O'Brien, KM; Olshan, AF; Olson, JE; Olsson, H; Orr, N; Perou, CM; Pita, G; Polley, EC; Prentice, RL; Rennert, G; Rennert, HS; Ruddy, KJ; Sandler, DP; Saunders, C; Schoemaker, MJ; Schöttker, B; Schumacher, F; Scott, C; Scott, RJ; Shu, X-O; Smeets, A; Southey, MC; Spinelli, JJ; Stone, J; Swerdlow, AJ; Tamimi, RM; Taylor, JA; Troester, MA; Vachon, CM; van Veen, EM; Wang, X; Weinberg, CR; Weltens, C; Willett, W; Winham, SJ; Wolk, A; Yang, XR; Zheng, W; Ziogas, A; Dunning, AM; Pharoah, PDP; Schmidt, MK; Kraft, P; Easton, DF; Milne, RL; García-Closas, M; Chang-Claude, J (2020-05-02)
    We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72,284 cases and 80,354 controls from the Breast Cancer ...

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