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Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers.
(NATURE PUBLISHING GROUP, 2018-05-01)
BACKGROUND: Proviral integration Moloney virus (PIM) kinases (PIM1, 2 and 3) are overexpressed in several tumour types and contribute to oncogenesis. AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated ...
Identification of highly penetrant Rb-related synthetic lethal interactions in triple negative breast cancer.
(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 ...
Mechanism-based screen establishes signalling framework for DNA damage-associated G1 checkpoint response.
(PUBLIC LIBRARY SCIENCE, 2012-02-27)
DNA damage activates checkpoint controls which block progression of cells through the division cycle. Several different checkpoints exist that control transit at different positions in the cell cycle. A role for checkpoint ...
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 ...
Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins.
(NATURE PUBLISHING GROUP, 2015-01-02)
The HSP90 molecular chaperone plays a key role in the maturation, stability and activation of its clients, including many oncogenic proteins. Kinases are a substantial and important subset of clients requiring the key ...
Characterisation of the immune-related transcriptome in resected biliary tract cancers.
(ELSEVIER SCI LTD, 2017-11-01)
UNLABELLED: Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune ...
A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events.
(CELL PRESS, 2017-10-25)
Protein complexes are responsible for the bulk of activities within the cell, but how their behavior and abundance varies across tumors remains poorly understood. By combining proteomic profiles of breast tumors with a ...
TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution.
(NATURE PUBLISHING GROUP, 2015-03-12)
During mitosis, sister chromatids must be faithfully segregated to ensure that daughter cells receive one copy of each chromosome. However, following replication they often remain entangled. Topoisomerase IIα (TOP2A) has ...
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 ...
Many private mutations originate from the first few divisions of a human colorectal adenoma.
(WILEY, 2015-11-01)
Intratumoural mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumour is commonly observed in human tumours. The mechanisms generating such ITH are uncertain. ...