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Functional screening reveals HORMAD1-driven gene dependencies associated with translesion synthesis and replication stress tolerance.
(SPRINGERNATURE, 2022-08-05)
HORMAD1 expression is usually restricted to germline cells, but it becomes mis-expressed in epithelial cells in ~60% of triple-negative breast cancers (TNBCs), where it is associated with elevated genomic instability (1). ...
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.
(AMER SOC CLINICAL INVESTIGATION INC, 2020-11-02)
The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show ...
Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer.
(PUBLIC LIBRARY SCIENCE, 2020-07-09)
Cyclin-dependent kinases (CDKs) contribute to the cancer hallmarks of uncontrolled proliferation and increased survival. As a result, over the last two decades substantial efforts have been directed towards identification ...
Evolution of kinase polypharmacology across HSP90 drug discovery.
(CELL PRESS, 2021-10-21)
Most small molecules interact with several target proteins but this polypharmacology is seldom comprehensively investigated or explicitly exploited during drug discovery. Here, we use computational and experimental methods ...
A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration.
(AMER ASSOC ADVANCEMENT SCIENCE, 2020-06-23)
Receptor tyrosine kinases (RTKs) are often overexpressed or mutated in cancers and drive tumor growth and metastasis. In the current model of RTK signaling, including that of MET, downstream phosphatidylinositol 3-kinase ...
Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness.
(NATURE PORTFOLIO, 2022-04-01)
Aneuploidy results in decreased cellular fitness in many species and model systems. However, aneuploidy is commonly found in cancer cells and often correlates with aggressive growth, suggesting that the impact of aneuploidy ...
Characterisation of the Stromal Microenvironment in Lobular Breast Cancer.
(MDPI, 2022-02-11)
Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma ...
EPEC-induced activation of the Ca2+ transporter TRPV2 leads to pyroptotic cell death.
(WILEY, 2022-02-01)
The enteropathogenic Escherichia coli (EPEC) type III secretion system effector Tir, which mediates intimate bacterial attachment to epithelial cells, also triggers Ca2+ influx followed by LPS entry and caspase-4-dependent ...
Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib).
(AMER ASSOC CANCER RESEARCH, 2022-04-14)
PURPOSE: Successful implementation of genomic testing in clinical practice is critical for identification of men with metastatic castration-resistant prostate cancer (mCRPC) eligible for olaparib and future molecularly ...