Browsing by author "Lord, Christopher"
Now showing items 1-20 of 97
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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 PRESS, 2017-10-25)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 ... -
A decade of clinical development of PARP inhibitors in perspective.
Mateo, J; Lord, CJ; Serra, V; Tutt, A; Balmaña, J; et al. (ELSEVIER, 2019-09-01)Genomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce ... -
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; et al. (AMER ASSOC CANCER RESEARCH, 2019-01-01)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 ... -
A Machine-Learning Tool Concurrently Models Single Omics and Phenome Data for Functional Subtyping and Personalized Cancer Medicine.
Nyamundanda, G; Eason, K; Guinney, J; Lord, CJ; Sadanandam, A (MDPI, 2020-09-30)One of the major challenges in defining clinically-relevant and less heterogeneous tumor subtypes is assigning biological and/or clinical interpretations to etiological (intrinsic) subtypes. Conventional clustering/subtyping ... -
A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors.
Menon, M; Elliott, R; Bowers, L; Balan, N; Rafiq, R; et al. (NATURE PUBLISHING GROUP, 2019-01-17)Inhibition of the PARP superfamily tankyrase enzymes suppresses Wnt/β-catenin signalling in tumour cells. Here, we describe here a novel, drug-like small molecule inhibitor of tankyrase MSC2504877 that inhibits the growth ... -
ADP-ribosyltransferases, an update on function and nomenclature.
Lüscher, B; Ahel, I; Altmeyer, M; Ashworth, A; Bai, P; et al. (WILEY, 2021-07-29)ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- ... -
Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors.
Neeb, A; Herranz, N; Arce-Gallego, S; Miranda, S; Buroni, L; et al. (ELSEVIER, 2020-11-08)BACKGROUND: Deleterious ATM alterations are found in metastatic prostate cancer (PC); PARP inhibition has antitumour activity against this subset, but only some ATM loss PCs respond. OBJECTIVE: To characterise ATM-deficient ... -
Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors.
Quigley, D; Alumkal, JJ; Wyatt, AW; Kothari, V; Foye, A; et al. (AMER ASSOC CANCER RESEARCH, 2017-09-01)Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination repair (HRR) such as BRCA2 HRR defects confer synthetic lethality to PARP inhibitors (PARPi) ... -
ATARI trial: ATR inhibitor in combination with olaparib in gynecological cancers with ARID1A loss or no loss (ENGOT/GYN1/NCRI).
Banerjee, S; Stewart, J; Porta, N; Toms, C; Leary, A; et al. (BMJ PUBLISHING GROUP, 2021-11-01)BACKGROUND: ARID1A (AT-rich interactive domain containing protein 1A) loss-of-function mutations have been reported in gynecological cancers, including rarer subtypes such as clear cell carcinoma. Preclinical studies ... -
ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A.
Williamson, CT; Miller, R; Pemberton, HN; Jones, SE; Campbell, J; et al. (NATURE PUBLISHING GROUP, 2016-12-13)Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations ... -
ATR Is a Therapeutic Target in Synovial Sarcoma.
Jones, SE; Fleuren, EDG; Frankum, J; Konde, A; Williamson, CT; et al. (AMER ASSOC CANCER RESEARCH, 2017-12-15)Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by expression of SS18-SSX fusions, where treatment options are limited. To identify therapeutically actionable genetic dependencies in SS, we ... -
Beyond DNA repair: the novel immunological potential of PARP inhibitors.
Chabanon, RM; Soria, J-C; Lord, CJ; Postel-Vinay, S (TAYLOR & FRANCIS INC, 2019-01-01)Loss of excision repair cross-complementation group 1 (ERCC1), frequently found in lung cancer, and mutations in breast cancer type 1/2 susceptibility genes (BRCA1/2), often found in ovarian, breast and prostate cancers, ... -
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial.
Carreira, S; Porta, N; Arce-Gallego, S; Seed, G; Llop-Guevara, A; et al. (AMER ASSOC CANCER RESEARCH, 2021-11-01)PARP inhibitors are approved for treating advanced prostate cancers (APC) with various defective DNA repair genes; however, further studies to clinically qualify predictive biomarkers are warranted. Herein we analyzed ... -
Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7.
Baxter, JS; Brough, R; Krastev, DB; Song, F; Sridhar, S; et al. (WILEY, 2023-10-22)The F-box and WD repeat domain containing 7 (FBXW7) tumour suppressor gene encodes a substrate-recognition subunit of Skp, cullin, F-box (SCF)-containing complexes. The tumour-suppressive role of FBXW7 is ascribed to its ... -
CancerGD: a resource for identifying and interpreting genetic dependencies in cancer
Bridgett, S; Campbell, J; Lord, C; Ryan, C (2016-10-26)Abstract Genes whose function is selectively essential in the presence of cancer associated genetic aberrations represent promising targets for the development of precision therapeutics. Here we present CancerGD ( ... -
CancerGD: A Resource for Identifying and Interpreting Genetic Dependencies in Cancer.
Bridgett, S; Campbell, J; Lord, CJ; Ryan, CJ (CELL PRESS, 2017-07-26)Genes whose function is selectively essential in the presence of cancer-associated genetic aberrations represent promising targets for the development of precision therapeutics. Here, we present CancerGD, a resource that ... -
CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours.
Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; et al. (PUBLIC LIBRARY SCIENCE, 2016-02-16)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 ... -
Cells Lacking the RB1 Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival.
Oser, MG; Fonseca, R; Chakraborty, AA; Brough, R; Spektor, A; et al. (AMER ASSOC CANCER RESEARCH, 2019-02-01)Small cell lung cancer (SCLC) accounts for 15% of lung cancers and is almost always linked to inactivating RB1 and TP53 mutations. SCLC frequently responds, albeit briefly, to chemotherapy. The canonical function of the ... -
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; et al. (WILEY, 2014-04-01)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 ... -
Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness.
Holme, H; Gulati, A; Brough, R; Fleuren, EDG; Bajrami, I; et al. (NATURE PUBLISHING GROUP, 2018-07-13)Osteosarcoma (OS) is an aggressive sarcoma, where novel treatment approaches are required. Genomic studies suggest that a subset of OS, including OS tumour cell lines (TCLs), exhibit genomic loss of heterozygosity (LOH) ...