Browsing Cancer Therapeutics by author "Lord, Christopher"
Now showing items 1-16 of 16
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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 ... -
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 ... -
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 PORTFOLIO, 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 ... -
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 ... -
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 ... -
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 ... -
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 ... -
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. ...