Browsing Clinical Studies by author "Lord, Christopher"
Now showing items 1-20 of 20
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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 ... -
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 ... -
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 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 ... -
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 ... -
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) ... -
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 ... -
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 ... -
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 ... -
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 ... -
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 ... -
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 ... -
MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma.
King, D; Li, XD; Almeida, GS; Kwok, C; Gravells, P; et al. (Impact Journals, LLC, 2020-06-09)This study investigates the influence expression of the MYCN oncogene has on the DNA damage response, replication fork progression and sensitivity to PARP inhibition in neuroblastoma. In a panel of neuroblastoma cell lines, ... -
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; et al. (AMER SOC CLINICAL ONCOLOGY, 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 ... -
Phase I Trial of the 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; et al. (AMER ASSOC CANCER RESEARCH, 2020-10-01)Preclinical studies have demonstrated synergy between PARP and PI3K/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing ... -
Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes.
Fleuren, EDG; Vlenterie, M; van der Graaf, WTA; Hillebrandt-Roeffen, MHS; Blackburn, J; et al. (AMER ASSOC CANCER RESEARCH, 2017-08-15)Despite intensive multimodal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical ... -
The Mutational Concordance of Fixed Formalin Paraffin Embedded and Fresh Frozen Gastro-Oesophageal Tumours Using Whole Exome Sequencing.
Chong, IY; Starling, N; Rust, A; Alexander, J; Aronson, L; et al. (MDPI, 2021-01-09)UNLABELLED: 1. BACKGROUND: The application of massively parallel sequencing has led to the identification of aberrant druggable pathways and somatic mutations within therapeutically relevant genes in gastro-oesophageal ... -
Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma.
George, SL; Lorenzi, F; King, D; Hartlieb, S; Campbell, J; et al. (ELSEVIER, 2020-09-01)BACKGROUND: In neuroblastoma, genetic alterations in ATRX, define a distinct poor outcome patient subgroup. Despite the need for new therapies, there is a lack of available models and a dearth of pre-clinical research. ...