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Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi-institutional retrospective study.
(ELSEVIER SCI LTD, 2018-03-01)
BACKGROUND: Most metastatic melanoma patients treated with BRAF inhibitors (BRAFi) ± MEK inhibitors (MEKi) eventually progress on treatment. Along with acquired resistance due to genetic changes, epigenetic mechanisms that ...
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 ...
Circulating Tumour DNA in Muscle-Invasive Bladder Cancer.
(MDPI, 2018-08-29)
Circulating tumour DNA (ctDNA) is an attractive tool in cancer research, offering many advantages over tissue samples obtained using traditional biopsy methods. There has been increasing interest in its application to ...
The shieldin complex mediates 53BP1-dependent DNA repair.
(NATURE PUBLISHING GROUP, 2018-08-02)
53BP1 is a chromatin-binding protein that regulates the repair of DNA double-strand breaks by suppressing the nucleolytic resection of DNA termini1,2. This function of 53BP1 requires interactions with PTIP3 and RIF14-9, ...
Nbeal2 interacts with Dock7, Sec16a, and Vac14.
(AMER SOC HEMATOLOGY, 2018-03-01)
Mutations in NBEAL2, the gene encoding the scaffolding protein Nbeal2, are causal of gray platelet syndrome (GPS), a rare recessive bleeding disorder characterized by platelets lacking α-granules and progressive marrow ...
Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.
(RADIOLOGICAL SOC NORTH AMERICA, 2018-09-01)
Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. ...