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  • Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance

    Therapies that target signalling molecules that are mutated in cancers can often have substantial short-term effects, but the emergence of resistant cancer cells is a major barrier to full cures1, 2. Resistance can result...

    Cancer

  • Single-molecule analysis of ligand efficacy in β2AR–G-protein activation

    G-protein-coupled receptor (GPCR)-mediated signal transduction is central to human physiology and disease intervention, yet the molecular mechanisms responsible for ligand-dependent signalling responses remain poorly understood. In class A GPCRs, receptor activation and G-protein coupling...

    cell signaling

  • Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer

    The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the...

    Cancer / New therapy

  • Tracking the Evolution of Non–Small-Cell Lung Cancer

    BACKGROUNDAmong patients with non–small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome...

    Cancer

  • Targeting PI3K Signaling in Combination Cancer Therapy

    Targeting upstream phosphatidylinositol-3-kinases (PI3Ks) in the PI3K/Akt/mTOR pathway appears to be a promising therapy in solid cancers; however, first early clinical trials with PI3K inhibitors in monotherapy have been disappointing. A massive array of...

    cell signaling / New therapy

  • Proteasome Activation by Small Molecules

    Highlights •Identification of more than ten small-molecule proteasome activators •Proteasome activators increase degradation of model substrates •P38 MAPK inhibition increases the clearance of toxic α-synuclein aggregates Summary Drugs that increase 26S proteasome activity have...

    Biochemistry

  • Cooking Up Cancer?

    In 1997, construction workers digging an 8.7-km railway tunnel in Sweden began experiencing unusual symptoms: nausea, dizziness, and numbness in their fingers. Around the same time, people living near the dig site discovered paralyzed...

    Cancer

  • Will Komodo Dragons Yield the Next Blockbuster Antibiotic?

    With the world facing an anti-biotic-resistance crisis, the hunt is on for alternatives to fight bacterial infection. The quest has led peptide chemist Barney Bishop and bacteriologist Monique van Hoek, both at George Mason...

    Biochemistry

  • Roadmaps for building the neonatal brain

    In the postnatal mammalian brain, neurons continue to be generated and migrate to their home stations. Often, these neuroblasts travel along pathways defined by the blood vessels or the glial cells that surround and...

    Neuroscience

  • The Exceptional Vulnerability of Humans to Alzheimer’s Disease

    Like many humans, non-human primates deposit copious misfolded Aβ protein in the brain as they age. Nevertheless, the complete behavioral and pathologic phenotype of Alzheimer’s disease, including Aβ plaques, neurofibrillary (tau) tangles, and dementia,...

    Neurobiochemistry / Neuroscience