ERK Inhibitor LY3214996 Targets ERK Pathway-Driven Cancers: A Therapeutic Approach Toward Precision Medicine.

The ERK pathway is critical in oncogenesis; aberrations in components of this pathway are common in approximately 30% of human cancers. ERK1/2 (ERK) regulates cell proliferation, differentiation, and survival and is the terminal node of the pathway. BRAF- and MEK-targeted therapies are effective in BRAF V600E/K metastatic melanoma and lung cancers; however, responses are short-lived due to emergence of resistance.

Abemaciclib Is Active in Preclinical Models of Ewing Sarcoma via Multipronged Regulation of Cell Cycle, DNA Methylation, and Interferon Pathway Signaling.

Purpose: Ewing sarcoma (ES) is a rare and highly malignant cancer that occurs in the bone and surrounding tissue of children and adolescents. The fusion transcription factor that drives ES pathobiology was previously demonstrated to modulate cyclin D1 expression. In this study, we evaluated abemaciclib, a small-molecule CDK4 and CDK6 (CDK4 and 6) inhibitor currently under clinical investigation in pediatric solid tumors, in preclinical models of ES.

A Method for Measuring the Weak Value of Spin for Metastable Atoms.

A method for measuring the weak value of spin for atoms is proposed using a variant of the original Stern-Gerlach apparatus. A full simulation of an experiment for observing the real part of the weak value using the impulsive approximation has been carried out. Our predictions show a displacement of the beam of helium atoms in the metastable 23S1 state, Δw, that is within the resolution of conventional microchannel plate detectors indicating that this type of experiment is feasible.

Feynman Paths and Weak Values.

There has been a recent revival of interest in the notion of a 'trajectory' of a quantum particle. In this paper, we detail the relationship between Dirac's ideas, Feynman paths and the Bohm approach. The key to the relationship is the weak value of the momentum which Feynman calls a transition probability amplitude.

Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine.

The G1 restriction point is critical for regulating the cell cycle and is controlled by the Rb pathway (CDK4/6-cyclin D1-Rb-p16/ink4a). This pathway is important because of its inactivation in a majority of human tumors. Transition through the restriction point requires phosphorylation of retinoblastoma protein (Rb) by CDK4/6, which are highly validated cancer drug targets.