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Modulation of Biliary Cancer Chemo-Resistance Through MicroRNA-Mediated Rewiring of the Expansion of CD133+ Cells.
(LIPPINCOTT WILLIAMS & WILKINS, 2020-09-10)
BACKGROUND AND AIMS: Changes in single microRNA (miRNA) expression have been associated with chemo-resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never ...
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
(AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-23)
Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ...
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 ...
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 ...
Molecular profiling and combinatorial activity of CCT068127: a potent CDK2 and CDK9 inhibitor.
(WILEY, 2018-03-01)
Deregulation of the cyclin-dependent kinases (CDKs) has been implicated in the pathogenesis of multiple cancer types. Consequently, CDKs have garnered intense interest as therapeutic targets for the treatment of cancer. ...
Modulation of Plasma Metabolite Biomarkers of the MAPK Pathway with MEK Inhibitor RO4987655: Pharmacodynamic and Predictive Potential in Metastatic Melanoma.
(AMER ASSOC CANCER RESEARCH, 2017-10-01)
MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based ...
Distinctive Behaviors of Druggable Proteins in Cellular Networks.
(PUBLIC LIBRARY SCIENCE, 2015-12-23)
The interaction environment of a protein in a cellular network is important in defining the role that the protein plays in the system as a whole, and thus its potential suitability as a drug target. Despite the importance ...
Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.
(AMER ASSOC CANCER RESEARCH, 2016-06-01)
PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and ...
Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology.
(CELL PRESS, 2017-07-10)
Small-molecule chemical probes or tools have become progressively more important in recent years as valuable reagents to investigate fundamental biological mechanisms and processes causing disease, including cancer. Chemical ...
SiGNet: A signaling network data simulator to enable signaling network inference.
(PUBLIC LIBRARY SCIENCE, 2017-05-17)
Network models are widely used to describe complex signaling systems. Cellular wiring varies in different cellular contexts and numerous inference techniques have been developed to infer the structure of a network from ...