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Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma.
(NATURE PUBLISHING GROUP, 2018-04-01)
Amplification of the locus encoding the oncogenic transcription factor MYCN is a defining feature of high-risk neuroblastoma. Here we present the first dynamic chromatin and transcriptional landscape of MYCN perturbation ...
EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer.
(NATURE PUBLISHING GROUP, 2017-12-11)
Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains ...
Objective, Quantitative, Data-Driven Assessment of Chemical Probes.
(CELL PRESS, 2018-02-15)
Chemical probes are essential tools for understanding biological systems and for target validation, yet selecting probes for biomedical research is rarely based on objective assessment of all potential compounds. Here, we ...
Combining Mutational Signatures, Clonal Fitness, and Drug Affinity to Define Drug-Specific Resistance Mutations in Cancer.
(CELL PRESS, 2018-11-15)
The emergence of mutations that confer resistance to molecularly targeted therapeutics is dependent upon the effect of each mutation on drug affinity for the target protein, the clonal fitness of cells harboring the mutation, ...
Leveraging Human Genetics to Guide Cancer Drug Development.
(AMER SOC CLINICAL ONCOLOGY, 2018-11-21)
PURPOSE: The high attrition rate of cancer drug development programs is a barrier to realizing the promise of precision oncology. We have examined whether the genetic insights from genome-wide association studies of cancer ...
Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates.
(AMER CHEMICAL SOC, 2018-09-21)
APOBEC3B (A3B) deamination activity on ssDNA is considered a contributing factor to tumor heterogeneity and drug resistance in a number of human cancers. Despite its clinical impact, little is known about A3B ssDNA substrate ...
Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma.
(NATURE PUBLISHING GROUP, 2018-10-30)
BACKGROUND: AKT is commonly overexpressed in tumours and plays an important role in the metabolic reprogramming of cancer. We have used magnetic resonance spectroscopy (MRS) to assess whether inhibition of AKT signalling ...
The long-term prognostic and predictive capacity of cyclin D1 gene amplification in 2305 breast tumours.
(BMC, 2019-02-28)
BACKGROUND: Use of cyclin D1 (CCND1) gene amplification as a breast cancer biomarker has been hampered by conflicting assessments of the relationship between cyclin D1 protein levels and patient survival. Here, we aimed ...
Rational design of non-resistant targeted cancer therapies.
(NATURE PORTFOLIO, 2017-04-24)
Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually ...
AMPK-independent inhibition of human macrophage ER stress response by AICAR.
(NATURE PORTFOLIO, 2016-08-26)
Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty ...