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Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737).
(AMER CHEMICAL SOC, 2016-06-09)
Multiparameter optimization of a series of 5-((4-aminopyridin-2-yl)amino)pyrazine-2-carbonitriles resulted in the identification of a potent and selective oral CHK1 preclinical development candidate with in vivo efficacy ...
High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial.
(AMER ASSOC CANCER RESEARCH, 2016-08-01)
UNLABELLED: FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level ...
Changes in Expression of Genes Representing Key Biologic Processes after Neoadjuvant Chemotherapy in Breast Cancer, and Prognostic Implications in Residual Disease.
(AMER ASSOC CANCER RESEARCH, 2016-05-15)
PURPOSE: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression of selected genes with ...
Hyperglycemia and Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) Inhibitors in Phase I Trials: Incidence, Predictive Factors, and Management.
(ALPHAMED PRESS, 2016-07-01)
BACKGROUND: Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is implicated in human cancer growth and progression. Agents targeting this pathway are ...
Lung stereotactic body radiotherapy with an MR-linac - Quantifying the impact of the magnetic field and real-time tumor tracking.
(ELSEVIER IRELAND LTD, 2016-06-01)
BACKGROUND AND PURPOSE: There are concerns that radiotherapy doses delivered in a magnetic field might be distorted due to the Lorentz force deflecting secondary electrons. This study investigates this effect on lung ...
Targeting the Human Epidermal Growth Factor Receptors with Immuno-PET: Imaging Biomarkers from Bench to Bedside.
(SOC NUCLEAR MEDICINE INC, 2016-07-01)
The Feasibility of Thermal Imaging as a Future Portal Imaging Device for Therapeutic Ultrasound.
(ELSEVIER SCIENCE INC, 2016-08-01)
This technical note describes a prototype thermally based portal imaging device that allows mapping of energy deposition on the surface of a tissue mimicking material in a focused ultrasound surgery (FUS) beam by using an ...
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease.
(AMER ASSOC ADVANCEMENT SCIENCE, 2016-06-01)
Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic ...
No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.
(BMJ PUBLISHING GROUP, 2016-05-01)
BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, ...
Clinical development of new drug-radiotherapy combinations.
(NATURE PUBLISHING GROUP, 2016-10-01)
In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures ...