Browsing by author "Lord, Christopher"
Now showing items 21-40 of 97
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Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival.
Tonnessen-Murray, CA; Frey, WD; Rao, SG; Shahbandi, A; Ungerleider, NA; et al. (ROCKEFELLER UNIV PRESS, 2019-11-04)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 ... -
Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition.
Goodall, J; Mateo, J; Yuan, W; Mossop, H; Porta, N; et al. (AMER ASSOC CANCER RESEARCH, 2017-09-01)Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity ... -
Clinical BRCA1/2 Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance.
Pettitt, SJ; Frankum, JR; Punta, M; Lise, S; Alexander, J; et al. (AMER ASSOC CANCER RESEARCH, 2020-10-01)Reversion mutations in BRCA1 or BRCA2 are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 reversions. This ... -
Clonal diversity of MYC amplification evaluated by fluorescent in situ hybridisation and digital droplet polymerase chain reaction in oesophagogastric cancer: Results from a prospective clinical trial screening programme.
Davidson, M; Aronson, LI; Howard-Reeves, J; Bryant, H; Cutts, RJ; et al. (ELSEVIER SCI LTD, 2019-11-01)INTRODUCTION: The MYC proto-oncogene is among the most commonly dysregulated genes in human cancers. We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced ... -
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; et al. (IMPACT JOURNALS LLC, 2015-05-10)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 ... -
COMPOUNDS AND THEIR USES
Newton, G; Lord, C; Ashworth, A; Perrior, T (2013-02-21)The invention provides a compound that is an inhibitor of one or both of TBK1 and IKKe, or a down-regulator of the expression of one or both of TBK1 and IKKe, for use in a method of treating a cancer that is dependent on ... -
Correction: CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours.
Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; et al. (2016-01) -
Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets.
Krastev, DB; Pettitt, SJ; Campbell, J; Song, F; Tanos, BE; et al. (NATURE PUBLISHING GROUP, 2018-05-22)Poly (ADP-ribose)ylation is a dynamic protein modification that regulates multiple cellular processes. Here, we describe a system for identifying and characterizing PARylation events that exploits the ability of a PBZ ... -
Cross-species identification of PIP5K1-, splicing- and ubiquitin-related pathways as potential targets for RB1-deficient cells.
Parkhitko, AA; Singh, A; Hsieh, S; Hu, Y; Binari, R; et al. (PUBLIC LIBRARY SCIENCE, 2021-02-16)The RB1 tumor suppressor is recurrently mutated in a variety of cancers including retinoblastomas, small cell lung cancers, triple-negative breast cancers, prostate cancers, and osteosarcomas. Finding new synthetic lethal ... -
Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.
Van Baelen, K; Geukens, T; Maetens, M; Tjan-Heijnen, V; Lord, CJ; et al. (ELSEVIER, 2022-08-01)BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ... -
DAISY: picking synthetic lethals from cancer genomes.
Ryan, CJ; Lord, CJ; Ashworth, A (CELL PRESS, 2014-09-08)A better understanding of genetic interactions in cancer might help identify new therapeutic approaches that exploit the concept of synthetic lethality. Ruppin and colleagues have developed a new computational method, ... -
De Novo Truncating Mutations in the Last and Penultimate Exons of PPM1D Cause an Intellectual Disability Syndrome.
Jansen, S; Geuer, S; Pfundt, R; Brough, R; Ghongane, P; et al. (CELL PRESS, 2017-04-06)Intellectual disability (ID) is a highly heterogeneous disorder involving at least 600 genes, yet a genetic diagnosis remains elusive in ∼35%-40% of individuals with moderate to severe ID. Recent meta-analyses statistically ... -
Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD.
Hewitt, G; Borel, V; Segura-Bayona, S; Takaki, T; Ruis, P; et al. (CELL PRESS, 2021-02-18)Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair ... -
Directing the use of DDR kinase inhibitors in cancer treatment.
Brandsma, I; Fleuren, EDG; Williamson, CT; Lord, CJ (TAYLOR & FRANCIS LTD, 2017-12-01)Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval of three different ... -
Dissecting PARP inhibitor resistance with functional genomics.
Pettitt, SJ; Lord, CJ (CURRENT BIOLOGY LTD, 2019-02-01)The poly-(ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib was the first licenced cancer drug that targeted an inherited form of cancer, namely ovarian cancers caused by germline BRCA1 or BRCA2 gene mutations. ... -
DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade.
Touat, M; Sourisseau, T; Dorvault, N; Chabanon, RM; Garrido, M; et al. (AMER SOC CLINICAL INVESTIGATION INC, 2018-04-02)Synthetic lethality is an efficient mechanism-based approach to selectively target DNA repair defects. Excision repair cross-complementation group 1 (ERCC1) deficiency is frequently found in non-small-cell lung cancer ... -
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.
Mateo, J; Carreira, S; Sandhu, S; Miranda, S; Mossop, H; et al. (MASSACHUSETTS MEDICAL SOC, 2015-10-29)BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would ... -
Driver Oncogenes but Not as We Know Them: Targetable Fusion Genes in Breast Cancer.
Natrajan, R; Tutt, ANJ; Lord, CJ (2018-03)<b/> Two reports in this issue of Cancer Discovery outline how the genomic composition of tumors, including the presence of intragenic gene fusions, could inform the selection of treatment approaches in aggressive forms ... -
E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.
Bajrami, I; Marlow, R; van de Ven, M; Brough, R; Pemberton, HN; et al. (AMER ASSOC CANCER RESEARCH, 2018-04-01)The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ... -
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; et al. (NATURE PUBLISHING GROUP, 2017-06-27)BACKGROUND: 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 ...