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Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study.
(2016-04)
<h4>Background</h4>Bromodomain and extraterminal (BET) proteins are chromatin readers that preferentially affect the transcription of genes with super-enhancers, including oncogenes. BET proteins bind acetylated histone ...
CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours.
(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 ...
Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells.
(NATURE PUBLISHING GROUP, 2018-08-01)
BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we conducted whole-genome ...
SF3B1 mutations constitute a novel therapeutic target in breast cancer.
(WILEY, 2015-03-01)
Mutations in genes encoding proteins involved in RNA splicing have been found to occur at relatively high frequencies in several tumour types including myelodysplastic syndromes, chronic lymphocytic leukaemia, uveal melanoma, ...
Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial.
(ELSEVIER SCIENCE INC, 2018-08-01)
BACKGROUND: Rhabdomyosarcoma is an aggressive tumour that can develop in almost any part of the body. Doxorubicin is an effective drug against rhabdomyosarcoma, but its role in combination with an established multidrug ...
Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept.
(AMER CHEMICAL SOC, 2018-08-23)
Structure-activity relationship and crystallographic data revealed that quinazolinone-containing fragments flip between two distinct modes of binding to activin receptor-like kinase-2 (ALK2). We explored both binding modes ...
MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.
(W B SAUNDERS CO-ELSEVIER INC, 2018-03-01)
BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA ...
Complementary genetic screens identify the E3 ubiquitin ligase CBLC, as a modifier of PARP inhibitor sensitivity.
(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 ...
Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib.
(AMER ASSOC CANCER RESEARCH, 2016-07-01)
New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based ...
Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts.
(IMPACT JOURNALS LLC, 2016-12-06)
The majority of breast cancers are estrogen receptor positive (ER+). Blockade of estrogen biosynthesis by aromatase inhibitors (AIs) is the first-line endocrine therapy for post-menopausal women with ER+ breast cancers. ...