Browsing by author "Lord, Christopher"
Now showing items 41-60 of 97
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Elucidating Prostate Cancer Behaviour During Treatment via Low-pass Whole-genome Sequencing of Circulating Tumour DNA.
Sumanasuriya, S; Seed, G; Parr, H; Christova, R; Pope, L; et al. (ELSEVIER, 2021-08-01)BACKGROUND: Better blood tests to elucidate the behaviour of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed to drive therapeutic decisions. Plasma cell-free DNA (cfDNA) comprises normal and ... -
European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer.
Vergote, I; González-Martín, A; Ray-Coquard, I; Harter, P; Colombo, N; et al. (ELSEVIER, 2022-03-01)BACKGROUND: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers ... -
Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer.
Naidoo, K; Wai, PT; Maguire, SL; Daley, F; Haider, S; et al. (AMER ASSOC CANCER RESEARCH, 2018-01-01)Disruption of Cyclin-Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. ... -
Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.
Baxter, JS; Johnson, N; Tomczyk, K; Gillespie, A; Maguire, S; et al. (CELL PRESS, 2021-07-01)A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), ... -
Functional screening reveals HORMAD1-driven gene dependencies associated with translesion synthesis and replication stress tolerance.
Tarantino, D; Walker, C; Weekes, D; Pemberton, H; Davidson, K; et al. (SPRINGERNATURE, 2022-08-05)HORMAD1 expression is usually restricted to germline cells, but it becomes mis-expressed in epithelial cells in ~60% of triple-negative breast cancers (TNBCs), where it is associated with elevated genomic instability (1). ... -
Functionally Null RAD51D Missense Mutation Associates Strongly with Ovarian Carcinoma.
Rivera, B; Di Iorio, M; Frankum, J; Nadaf, J; Fahiminiya, S; et al. (AMER ASSOC CANCER RESEARCH, 2017-08-15)RAD51D is a key player in DNA repair by homologous recombination (HR), and RAD51D truncating variant carriers have an increased risk for ovarian cancer. However, the contribution of nontruncating RAD51D variants to cancer ... -
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
Pettitt, SJ; Krastev, DB; Brandsma, I; Dréan, A; Song, F; et al. (NATURE PUBLISHING GROUP, 2018-05-01)Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ... -
Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells.
Pettitt, SJ; Krastev, DB; Pemberton, HN; Fontebasso, Y; Frankum, J; et al. (NATURE PUBLISHING GROUP, 2017-03-01)We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 ... -
Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress.
McDade, SS; Patel, D; Moran, M; Campbell, J; Fenwick, K; et al. (OXFORD UNIV PRESS, 2014-01-01)In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by ... -
HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer.
Brunton, H; Caligiuri, G; Cunningham, R; Upstill-Goddard, R; Bailey, U-M; et al. (CELL PRESS, 2020-05-12)Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic ... -
A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.
Pettitt, SJ; Shao, N; Zatreanu, D; Frankum, J; Bajrami, I; et al. (SPRINGERNATURE, 2023-09-01)Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, ... -
Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance.
Serra, V; Wang, AT; Castroviejo-Bermejo, M; Polanska, UM; Palafox, M; et al. (AMER ASSOC CANCER RESEARCH, 2022-10-14)PURPOSE: PARP inhibitors (PARPi) induce synthetic lethality in homologous recombination repair (HRR)-deficient tumors and are used to treat breast, ovarian, pancreatic, and prostate cancers. Multiple PARPi resistance ... -
Identification of highly penetrant Rb-related synthetic lethal interactions in triple negative breast cancer.
Brough, R; Gulati, A; Haider, S; Kumar, R; Campbell, J; et al. (NATURE PUBLISHING GROUP, 2018-10-25)Although defects in the RB1 tumour suppressor are one of the more common driver alterations found in triple-negative breast cancer (TNBC), therapeutic approaches that exploit this have not been identified. By integrating ... -
Identifying Genetic Dependencies in Cancer by Analyzing siRNA Screens in Tumor Cell Line Panels.
Campbell, J; Ryan, CJ; Lord, CJ (HUMANA PRESS INC, 2018-01-01)Loss-of-function screening using RNA interference or CRISPR approaches can be used to identify genes that specific tumor cell lines depend upon for survival. By integrating the results from screens in multiple cell lines ... -
Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer.
Nava Rodrigues, D; Rescigno, P; Liu, D; Yuan, W; Carreira, S; et al. (AMER SOC CLINICAL INVESTIGATION INC, 2018-10-01)BACKGROUND: Understanding the integrated immunogenomic landscape of advanced prostate cancer (APC) could impact stratified treatment selection. METHODS: Defective mismatch repair (dMMR) status was determined by either loss ... -
Integrative analysis of large-scale loss-of-function screens identifies robust cancer-associated genetic interactions.
Lord, CJ; Quinn, N; Ryan, CJ (ELIFE SCIENCES PUBLICATIONS LTD, 2020-05-28)Genetic interactions, including synthetic lethal effects, can now be systematically identified in cancer cell lines using high-throughput genetic perturbation screens. Despite this advance, few genetic interactions have ... -
Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines.
Campbell, J; Ryan, CJ; Brough, R; Bajrami, I; Pemberton, HN; et al. (CELL PRESS, 2016-03-15)One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase ... -
Longitudinal analysis of a secondary BRCA2 mutation using digital droplet PCR.
Khalique, S; Pettitt, SJ; Kelly, G; Tunariu, N; Natrajan, R; et al. (WILEY, 2019-11-20)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 ... -
Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.
Harvey-Jones, E; Raghunandan, M; Robbez-Masson, L; Magraner-Pardo, L; Alaguthurai, T; et al. (Elsevier BV, 2024-01-19)BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, ... -
Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer.
Chong, IY; Aronson, L; Bryant, H; Gulati, A; Campbell, J; et al. (BMJ PUBLISHING GROUP, 2018-10-01)OBJECTIVE: Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. DESIGN: To identify new biomarker-defined therapeutic approaches ...