Search
Now showing items 1-10 of 26
Dual blockade of the PI3K/AKT/mTOR (AZD8055) and RAS/MEK/ERK (AZD6244) pathways synergistically inhibits rhabdomyosarcoma cell growth in vitro and in vivo.
(AMER ASSOC CANCER RESEARCH, 2013-08-05)
PURPOSE: To provide rationale for using phosphoinositide 3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathway inhibitors to treat rhabdomyosarcomas, a major cause of pediatric and adolescent cancer deaths. ...
GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors.
(AMER ASSOC CANCER RESEARCH, 2013-06-15)
Most breast cancers at diagnosis are estrogen receptor-positive (ER(+)) and depend on estrogen for growth and survival. Blocking estrogen biosynthesis by aromatase inhibitors has therefore become a first-line endocrine ...
The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles.
(NATURE PUBLISHING GROUP, 2016-03-10)
Caspases provide vital links in non-apoptotic regulatory networks controlling inflammation, compensatory proliferation, morphology and cell migration. How caspases are activated under non-apoptotic conditions and process ...
Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors.
(IMPACT JOURNALS LLC, 2016-09-06)
MYC oncoproteins deliver a potent oncogenic stimulus in several human cancers, making them major targets for drug development, but efforts to deliver clinically practical therapeutics have not yet been realized. In childhood ...
Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma.
(NATURE PUBLISHING GROUP, 2020-03-01)
High-grade glioma (HGG) is highly resistant to therapy, prompting us to investigate the contribution of insulin-like growth factor receptor (IGF-1R), linked with radioresistance in other cancers. IGF-1R immunohistochemistry ...
Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's Cytotoxic Potential.
(CELL PRESS, 2018-04-10)
Tumor necrosis factor (TNF) is an inflammatory cytokine that can signal cell survival or cell death. The mechanisms that switch between these distinct outcomes remain poorly defined. Here, we show that the E3 ubiquitin ...
BRD4 facilitates replication stress-induced DNA damage response.
(NATURE PUBLISHING GROUP, 2018-07-12)
Previous reports have demonstrated that select cancers depend on BRD4 to regulate oncogenic gene transcriptional programs. Here we describe a novel role for BRD4 in DNA damage response (DDR). BRD4 associates with and ...
Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2019-08-01)
It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic ...
Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment.
(NATURE PORTFOLIO, 2018-08-09)
Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered ...
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.
(NATURE PUBLISHING GROUP, 2019-06-13)
Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that ...