A human metabolic map of pharmacological perturbations reveals drug modes of action.

Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.

Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus.

Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into the infant intestine through breast milk could provide enhanced antimicrobial protection for neonates.

A novel clinical brain prognostic index for KRAS-mutated lung cancer and brain metastases (KRAS-BPI): Real-world evidence from two large European centers.

Introduction: Several prognostic scores were developed for non-small-cell lung cancer (NSCLC) patients with brain metastases (BM), though limited data reported for the KRAS-mutated subgroup. KRAS-targeted therapies have improved extracranial and intracranial response, highlighting the need for reliable prognostic biomarkers.

Methods: A retrospective cohort (2010-2020) comprising 220 patients with BM KRAS-mutated NSCLC from two large academic Thoracic Oncology centers (Karolinska and Heidelberg) was analyzed.