Now showing items 1-20 of 46

    • ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942. 

      Sava, GP; Fan, H; Fisher, RA; Lusvarghi, S; Pancholi, S; Ambudkar, SV; Martin, L-A; Charles Coombes, R; Buluwela, L; Ali, S (2020-01)
      The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become ...
    • Abiraterone shows alternate activity in models of endocrine resistant and sensitive disease. 

      Simigdala, N; Pancholi, S; Ribas, R; Folkerd, E; Liccardi, G; Nikitorowicz-Buniak, J; Johnston, SR; Dowsett, M; Martin, L-A (2018-08)
      <h4>Background</h4>Resistance to endocrine therapy remains a major clinical problem in the treatment of oestrogen-receptor positive (ER+) breast cancer. Studies show androgen-receptor (AR) remains present in 80-90% of ...
    • Association of p27 and Cyclin D1 Expression and Benefit from Adjuvant Trastuzumab Treatment in HER2-Positive Early Breast Cancer: A TransHERA Study. 

      Filipits, M; Dafni, U; Gnant, M; Polydoropoulou, V; Hills, M; Kiermaier, A; de Azambuja, E; Larsimont, D; Rojo, F; Viale, G; Toi, M; Harbeck, N; Prichard, KI; Gelber, RD; Dinh, P; Zardavas, D; Leyland-Jones, B; Piccart-Gebhart, MJ; Dowsett, M; TransHERA investigators (2018-07)
      Purpose: To assess the prognostic and predictive value of selected biomarkers involved in cell-cycle regulation or proliferation in patients with HER2-positive early breast cancer.Experimental Design: Protein expression ...
    • Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. 

      Dunning, AM; Michailidou, K; Kuchenbaecker, KB; Thompson, D; French, JD; Beesley, J; Healey, CS; Kar, S; Pooley, KA; Lopez-Knowles, E; Dicks, E; Barrowdale, D; Sinnott-Armstrong, NA; Sallari, RC; Hillman, KM; Kaufmann, S; Sivakumaran, H; Moradi Marjaneh, M; Lee, JS; Hills, M; Jarosz, M; Drury, S; Canisius, S; Bolla, MK; Dennis, J; Wang, Q; Hopper, JL; Southey, MC; Broeks, A; Schmidt, MK; Lophatananon, A; Muir, K; Beckmann, MW; Fasching, PA; Dos-Santos-Silva, I; Peto, J; Sawyer, EJ; Tomlinson, I; Burwinkel, B; Marme, F; Guénel, P; Truong, T; Bojesen, SE; Flyger, H; González-Neira, A; Perez, JIA; Anton-Culver, H; Eunjung, L; Arndt, V; Brenner, H; Meindl, A; Schmutzler, RK; Brauch, H; Hamann, U; Aittomäki, K; Blomqvist, C; Ito, H; Matsuo, K; Bogdanova, N; Dörk, T; Lindblom, A; Margolin, S; Kosma, V-M; Mannermaa, A; Tseng, C-C; Wu, AH; Lambrechts, D; Wildiers, H; Chang-Claude, J; Rudolph, A; Peterlongo, P; Radice, P; Olson, JE; Giles, GG; Milne, RL; Haiman, CA; Henderson, BE; Goldberg, MS; Teo, SH; Yip, CH; Nord, S; Borresen-Dale, A-L; Kristensen, V; Long, J; Zheng, W; Pylkäs, K; Winqvist, R; Andrulis, IL; Knight, JA; Devilee, P; Seynaeve, C; Figueroa, J; Sherman, ME; Czene, K; Darabi, H; Hollestelle, A; van den Ouweland, AMW; Humphreys, K; Gao, Y-T; Shu, X-O; Cox, A; Cross, SS; Blot, W; Cai, Q; Ghoussaini, M; Perkins, BJ; Shah, M; Choi, J-Y; Kang, D; Lee, SC; Hartman, M; Kabisch, M; Torres, D; Jakubowska, A; Lubinski, J; Brennan, P; Sangrajrang, S; Ambrosone, CB; Toland, AE; Shen, C-Y; Wu, P-E; Orr, N; Swerdlow, A; McGuffog, L; Healey, S; Lee, A; Kapuscinski, M; John, EM; Terry, MB; Daly, MB; Goldgar, DE; Buys, SS; Janavicius, R; Tihomirova, L; Tung, N; Dorfling, CM; van Rensburg, EJ; Neuhausen, SL; Ejlertsen, B; Hansen, TVO; Osorio, A; Benitez, J; Rando, R; Weitzel, JN; Bonanni, B; Peissel, B; Manoukian, S; Papi, L; Ottini, L; Konstantopoulou, I; Apostolou, P; Garber, J; Rashid, MU; Frost, D; EMBRACE; Izatt, L; Ellis, S; Godwin, AK; Arnold, N; Niederacher, D; Rhiem, K; Bogdanova-Markov, N; Sagne, C; Stoppa-Lyonnet, D; Damiola, F; GEMO Study Collaborators; Sinilnikova, OM; Mazoyer, S; Isaacs, C; Claes, KBM; De Leeneer, K; de la Hoya, M; Caldes, T; Nevanlinna, H; Khan, S; Mensenkamp, AR; HEBON; Hooning, MJ; Rookus, MA; Kwong, A; Olah, E; Diez, O; Brunet, J; Pujana, MA; Gronwald, J; Huzarski, T; Barkardottir, RB; Laframboise, R; Soucy, P; Montagna, M; Agata, S; Teixeira, MR; kConFab Investigators; Park, SK; Lindor, N; Couch, FJ; Tischkowitz, M; Foretova, L; Vijai, J; Offit, K; Singer, CF; Rappaport, C; Phelan, CM; Greene, MH; Mai, PL; Rennert, G; Imyanitov, EN; Hulick, PJ; Phillips, K-A; Piedmonte, M; Mulligan, AM; Glendon, G; Bojesen, A; Thomassen, M; Caligo, MA; Yoon, S-Y; Friedman, E; Laitman, Y; Borg, A; von Wachenfeldt, A; Ehrencrona, H; Rantala, J; Olopade, OI; Ganz, PA; Nussbaum, RL; Gayther, SA; Nathanson, KL; Domchek, SM; Arun, BK; Mitchell, G; Karlan, BY; Lester, J; Maskarinec, G; Woolcott, C; Scott, C; Stone, J; Apicella, C; Tamimi, R; Luben, R; Khaw, K-T; Helland, Å; Haakensen, V; Dowsett, M; Pharoah, PDP; Simard, J; Hall, P; García-Closas, M; Vachon, C; Chenevix-Trench, G; Antoniou, AC; Easton, DF; Edwards, SL (2016-04)
      We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each ...
    • CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours. 

      Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; Marinari, E; Riffell, J; Bardelli, A; Torrance, C; Lord, CJ; Ashworth, A (2016-01)
      Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent ...
    • Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast. 

      Natrajan, R; Wilkerson, PM; Marchiò, C; Piscuoglio, S; Ng, CKY; Wai, P; Lambros, MB; Samartzis, EP; Dedes, KJ; Frankum, J; Bajrami, I; Kopec, A; Mackay, A; A'hern, R; Fenwick, K; Kozarewa, I; Hakas, J; Mitsopoulos, C; Hardisson, D; Lord, CJ; Kumar-Sinha, C; Ashworth, A; Weigelt, B; Sapino, A; Chinnaiyan, AM; Maher, CA; Reis-Filho, JS (2014-04)
      Micropapillary carcinoma (MPC) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations (CNAs) distinct from that of grade- and oestrogen ...
    • Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer. 

      Simigdala, N; Gao, Q; Pancholi, S; Roberg-Larsen, H; Zvelebil, M; Ribas, R; Folkerd, E; Thompson, A; Bhamra, A; Dowsett, M; Martin, L-A (2016-06)
      <h4>Background</h4>Therapies targeting estrogenic stimulation in estrogen receptor-positive (ER+) breast cancer (BC) reduce mortality, but resistance remains a major clinical problem. Molecular studies have shown few ...
    • Comparison of protein expression between formalin-fixed core-cut biopsies and surgical excision specimens using a novel multiplex approach. 

      Leal, MF; Haynes, BP; MacNeill, FA; Dodson, A; Dowsett, M (2019-06)
      <h4>Purpose</h4>We evaluated whether multiplex protein quantification using antibody bar-coding with photocleavable oligonucleotides (NanoString) can be applied to evaluate protein expression in breast cancer FFPE specimens. ...
    • Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. 

      Sestak, I; Buus, R; Cuzick, J; Dubsky, P; Kronenwett, R; Denkert, C; Ferree, S; Sgroi, D; Schnabel, C; Baehner, FL; Mallon, E; Dowsett, M (2018-04)
      Importance:Multiple molecular signatures are available for managing estrogen receptor (ER)-positive breast cancer but with little direct comparative information to guide the patient's choice. Objective:To conduct a ...
    • A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events. 

      Ryan, CJ; Kennedy, S; Bajrami, I; Matallanas, D; Lord, CJ (2017-10-11)
      Protein complexes are responsible for the bulk of activities within the cell, but how their behavior and abundance varies across tumors remains poorly understood. By combining proteomic profiles of breast tumors with a ...
    • Complementary genetic screens identify the E3 ubiquitin ligase CBLC, as a modifier of PARP inhibitor sensitivity. 

      Frankum, J; Moudry, P; Brough, R; Hodny, Z; Ashworth, A; Bartek, J; Lord, CJ (2015-05)
      Based on a series of basic, preclinical and clinical studies, the Poly (ADP-ribose) Polymerase 1 (PARP1) inhibitor, olaparib, has recently been approved for use in ovarian cancer patients with BRCA1 or BRCA2 mutations. By ...
    • DNA methylation of the long intergenic noncoding RNA 299 gene in triple-negative breast cancer: results from a prospective study. 

      Manoochehri, M; Jones, M; Tomczyk, K; Fletcher, O; Schoemaker, MJ; Swerdlow, AJ; Borhani, N; Hamann, U (2020-07-16)
      Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with a high rate of recurrence and poor prognosis. Recently we identified a hypermethylation in the long noncoding RNA 299 (LINC00299) ...
    • Early Enrichment of ESR1 Mutations and the Impact on Gene Expression in Presurgical Primary Breast Cancer Treated with Aromatase Inhibitors. 

      Leal, MF; Haynes, BP; Schuster, E; Yeo, B; Afentakis, M; Zabaglo, L; Martins, V; Buus, R; Dodson, A; Cheang, MCU; Smith, IE; Martin, L-A; Dowsett, M (2019-12)
      PURPOSE:To investigate the presence of ESR1 mutations in primary estrogen-receptor-positive (ER+) breast cancer treated with extended (>4 weeks) neoadjuvant (presurgical) aromatase inhibitor (NAI) therapy and to identify ...
    • Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells. 

      Nikkilä, J; Kumar, R; Campbell, J; Brandsma, I; Pemberton, HN; Wallberg, F; Nagy, K; Scheer, I; Vertessy, BG; Serebrenik, AA; Monni, V; Harris, RS; Pettitt, SJ; Ashworth, A; Lord, CJ (2017-06)
      Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 status on ...
    • Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. 

      Xiao, T; Li, W; Wang, X; Xu, H; Yang, J; Wu, Q; Huang, Y; Geradts, J; Jiang, P; Fei, T; Chi, D; Zang, C; Liao, Q; Rennhack, J; Andrechek, E; Li, N; Detre, S; Dowsett, M; Jeselsohn, RM; Liu, XS; Brown, M (2018-07-09)
      Endocrine therapy resistance invariably develops in advanced estrogen receptor-positive (ER+) breast cancer, but the underlying mechanisms are largely unknown. We have identified C-terminal SRC kinase (CSK) as a critical ...
    • Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. 

      Aarts, M; Sharpe, R; Garcia-Murillas, I; Gevensleben, H; Hurd, MS; Shumway, SD; Toniatti, C; Ashworth, A; Turner, NC (2012-06)
      Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. Here, we investigate the mechanism that underlies this synergy. ...
    • A Four-gene Decision Tree Signature Classification of Triple-negative Breast Cancer: Implications for Targeted Therapeutics. 

      Quist, J; Mirza, H; Cheang, MCU; Telli, ML; O'Shaughnessy, JA; Lord, CJ; Tutt, ANJ; Grigoriadis, A (2019-01)
      The molecular complexity of triple-negative breast cancers (TNBCs) provides a challenge for patient management. We set out to characterize this heterogeneous disease by combining transcriptomics and genomics data, with the ...
    • From integrative genomics to therapeutic targets. 

      Natrajan, R; Wilkerson, P (2013-06-05)
      Combinatorial approaches that integrate conventional pathology with genomic profiling and functional genomics have begun to enhance our understanding of the genetic basis of breast cancer. These methods have identified key ...
    • GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. 

      Morandi, A; Martin, L-A; Gao, Q; Pancholi, S; Mackay, A; Robertson, D; Zvelebil, M; Dowsett, M; Plaza-Menacho, I; Isacke, CM (2013-06)
      Most breast cancers at diagnosis are estrogen receptor-positive (ER(+)) and depend on estrogen for growth and survival. Blocking estrogen biosynthesis by aromatase inhibitors has therefore become a first-line endocrine ...
    • Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study. 

      Lawler, K; Papouli, E; Naceur-Lombardelli, C; Mera, A; Ougham, K; Tutt, A; Kimbung, S; Hedenfalk, I; Zhan, J; Zhang, H; Buus, R; Dowsett, M; Ng, T; Pinder, SE; Parker, P; Holmberg, L; Gillett, CE; Grigoriadis, A; Purushotham, A (2017-10-13)
      Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited.A ...