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Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma.
(AMER ASSOC CANCER RESEARCH, 2016-01-01)
Sunitinib and pazopanib are antiangiogenic tyrosine kinase inhibitors (TKI) used to treat metastatic renal cell carcinoma (RCC). However, the ability of these drugs to extend progression-free and overall survival in this ...
Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma.
(CELL PRESS, 2015-01-12)
BRAF and MEK inhibitors are effective in BRAF mutant melanoma, but most patients eventually relapse with acquired resistance, and others present intrinsic resistance to these drugs. Resistance is often mediated by pathway ...
Computational pathology: Exploring the spatial dimension of tumor ecology.
(ELSEVIER IRELAND LTD, 2016-09-28)
Tumors are evolving ecosystems where cancer subclones and the microenvironment interact. This is analogous to interaction dynamics between species in their natural habitats, which is a prime area of study in ecology. Spatial ...
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 ...
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.
(NATURE RESEARCH, 2021-06-17)
To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ...
Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19.
(AMER CHEMICAL SOC, 2016-02-11)
The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 ...
Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
(AMER CHEMICAL SOC, 2016-10-27)
The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development ...
Cells Lacking the RB1 Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival.
(AMER ASSOC CANCER RESEARCH, 2019-02-01)
Small cell lung cancer (SCLC) accounts for 15% of lung cancers and is almost always linked to inactivating RB1 and TP53 mutations. SCLC frequently responds, albeit briefly, to chemotherapy. The canonical function of the ...
The Citrobacter rodentium type III secretion system effector EspO affects mucosal damage repair and antimicrobial responses.
(PUBLIC LIBRARY SCIENCE, 2018-10-01)
Infection with Citrobacter rodentium triggers robust tissue damage repair responses, manifested by secretion of IL-22, in the absence of which mice succumbed to the infection. Of the main hallmarks of C. rodentium infection ...
Maternal and fetal cardiometabolic recovery following ultrasound-guided high-intensity focused ultrasound placental vascular occlusion.
(ROYAL SOC, 2019-05-31)
High-intensity focused ultrasound (HIFU) is a non-invasive method of selective placental vascular occlusion, providing a potential therapy for conditions such as twin-twin transfusion syndrome. In order to translate this ...