The hype surrounding artificial intelligence (AI) can make it sound like the technology has all the answers. But from a scientific perspective, one of the technology's biggest strengths is that it can ask better questions.
TRK inhibitors, like essentially all targeted therapies, are vulnerable to resistance mutations, and several resistance mutations to Vitrakvi and the recently approved Rozlytrek have been described. The most common form of resistance to targeted therapies, and the only mechanisms that have been described for TRK inhibitors to date, are due to mutations in the target itself. Now, researchers at Memorial Sloan-Kettering Cancer Center have described resistance to TRK inhibitors that occurred due to activation of the MAP kinase (MAPK) pathway.
Investigators at Stanford University have created a panel of isogenic iPSC-derived neurons with various mutations of amyloid precursor protein (APP) and presenilin (PSEN), and used it to demonstrate that accumulation of APP beta C-terminal fragments (beta-CTFs), but not of amyloid beta, correlated with endosomal dysfunction and could be improved by inhibiting beta-secretase (BACE-1). Genetic evidence clearly implicates APP misprocessing in Alzheimer's disease (AD), and amyloid beta plaques are the disease's major anatomical calling card, which has led to a focus on therapeutic targeting of the latter. However, that therapeutic targeting has failed multiple times, and the evidence linking amyloid beta to AD is weaker than that for APP. Recently, endosomal dysfunction has been proposed as "another plausible underlying pathological mechanism," leading the authors to investigate the causes of endosomal dysfunction in their cell lines. They showed that endosomal dysfunction, which leads to deficits in intracellular transport, was correlated with changes in beta-CTF but not amyloid beta.
The blood-brain barrier prevents many drugs from entering the brain. Unfortunately, the same cannot be said for tumor cells. The brain is one of the most frequent locations for cancer metastases, which are then extremely challenging to treat. Now, researchers at the University of California at Los Angeles have developed an encapsulation technique that allowed the delivery of the monoclonal antibody Rituxan (rituximab) to brain metastases of a mouse xenograft model of non-Hodgkin lymphoma.
The microbiome has broad and deep effects on pretty much all aspects of health. So broad and so deep, in fact, that how to best translate those effects into medical interventions remains an open question.
As shown most spectacularly by the fireworks-like rise and explosion of Theranos, there is an urgent need for diagnostics that can detect very low amounts of their targets in very small sample volumes. Amplification systems exist for nucleic acids, but not for proteins. Now, researchers from the Massachusetts Institute of Technology have developed a method, which they have termed hierarchical nanofluidic molecular enrichment system (HOLMES) – named, one hopes, for Sherlock, not Elizabeth – for amplification of very low concentrations of solutes from fluids, including blood serum and urine.
Scientists from University Hospital Freiburg and the NIH have created mice that combine "microbiota and pathogens at all body sites and the tractable genetics of C57BL/6 mice."
Sexual dimorphism in gene expression is widespread across chromosomes, and is partially conserved across species from mice to humans, the first study to investigate such differences both across species and across tissues has found.
