Volume 24 Issue 7, July 2018

Nationwide trials pair children with targeted cancer therapies.

First-of-its-kind US trial hopes to bring hospital treatment to the home.

The pathological hallmarks of Alzheimer’s disease (AD) include extracellular beta-amyloid plaques, neurofibrillary tangles, neuronal loss and tau deposits in brain. Therapies targeting these known hallmarks are yet to yield any meaningful benefit in clinical trials. We spoke to four researchers in the fields of AD research and therapy development to find out where they think the fields should head next.

Signaling by the tumor-suppressor protein p53 antagonizes CRISPR–Cas9 gene editing of human pluripotent stem cells and immortalized human retinal pigment epithelial cells.

A glucagon-like peptide receptor 1 (GLP-1R) agonist inhibits the conversion of astrocytes into a neurotoxic phenotype and protects against neurodegeneration, shedding light on the pathogenesis of Parkinson’s disease.

Studies in KRAS-mutant lung and pancreatic adenocarcinoma and in KRAS-amplified gastric carcinoma reveal that SHP2 inhibition augments the antitumor effect of MEK inhibitor treatment.

The number, identity, and burden of mutations in clonal hematopoiesis are associated with the risk and timing of progression to acute myeloid leukemia.

An integrative multiomics approach in nondiabetic obese women identifies phenylacetate as a microbial metabolite contributing to the accumulation of lipids in the liver and hence to nonalcoholic steatohepatitis.

Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials.

Initiation of antiretroviral therapy in the first 2 weeks of HIV infection fails to prevent resurgence of virus after stopping treatment, indicating early establishment of a resilient viral reservoir.

CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in immortalized human retinal pigment epithelial cells.

Agonism of microglial glucagon-like peptide-1 receptor (GLP1R) using a brain-penetrant peptide prevents the generation of neurotoxic astrocytes and ameliorates disease progression in two rodent models of Parkinson’s disease.

CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in human pluripotent cells.

In vivo shRNA screens in sensitized genetic backgrounds identify p53-activated target genes involved in DNA repair that enable its tumor suppressor function.

The phosphatase SHP2 is required for mutant KRAS signaling in pancreatic and non-small-cell lung cancers and drives resistance to MEK inhibition.

Combined inhibition of SHP2 and MEK is an effective therapeutic approach in non-small-cell lung cancer.

Amplification of wild-type KRAS in a subset of gastroesophageal tumors drives intrinsic resistance to MAPK inhibition that can be overcome by combined targeting of MEK and SHP2.

Deep single-cell RNA sequencing of tumor-infiltrating T cells in non-small-cell lung cancer identifies features associated with functional states and clinical outcome

Extensive, high-dimensional characterization of T cells in breast cancer reveals activated T_RM population and a gene signature associated with improved prognosis.

Tumor-infiltrating CD8⁺ T cells with high expression of PD-1 in non-small-cell lung cancer are distinct from exhausted T cells in chronic virus infection, have high tumor reactivity and associate with response to PD-1-targeted immunotherapy.

A human anti-IL-2 antibody that selectively expands regulatory T cells is developed in this study for clinical applications aiming to mitigate autoimmune and inflammatory disorders and to promote transplant tolerance.

Somatic mutations detected years before diagnosis increase the odds of development of acute myeloid leukemia in women.

Reactive astrocytes expressing STAT3 support the metastatic growth of tumor cells colonizing the brain and can be pharmacologically targeted to improve the clinical management of patients with secondary brain tumors.

A new inhibitor targeting the mitochondrial complex I shows antitumor activity in preclinical models of acute myeloid leukemia and glioblastoma relying on oxidative phosphorylation.

SMARCA4 loss in non-small-cell lung cancer creates a metabolic dependency on oxidative phosphorylation that can be targeted using a new small-molecule inhibitor.

Follistatin acts as a hepatokine to induce insulin resistance and can be targeted to improve diabetes in mice.

Metabolic activity of specific human gut microorganisms contributes to liver steatosis in obese women.