Aberrant Lung Cells Drive Fibrosis Progression
Journal: Nat Commun 16, 8710 (2025).
Author: Hoffman, E.T., Shah, A., Barboza, W.R. et al., USA
New research uncovers how intermediate alveolar epithelial cells fuel pulmonary fibrosis (PF). Using a genetic mouse model and patient-derived stem cell models, scientists showed that dysfunctional AT2 cells adopt an aberrant basaloid-like state. These cells release a TGF-β–driven profibrotic secretome that activates fibroblasts, while losing normal progenitor signals that would maintain healthy repair. The findings highlight aberrant epithelial–fibroblast crosstalk as a key driver of PF and a potential therapeutic target.
Exosome Therapy Shows Promise in Pancreatic Cancer
Journal: Nat Commun 16, 8696 (2025).
Author: Kalluri, V.S., Smaglo, B.G., Mahadevan, K.K. et al., USA
A Phase I clinical trial (iEXPLORE) tested engineered exosomes carrying KRASG12D-specific siRNA in patients with advanced pancreatic cancer. The treatment was well-tolerated with no dose-limiting toxicity, and some patients achieved stable disease. Molecular analyses showed KRASG12D suppression, reduced phospho-ERK signaling, and increased CD8+ T cell infiltration, suggesting immune activation. Preclinical studies further revealed that combining this therapy with anti-CTLA-4 antibodies boosted anti-tumor activity, pointing to a potential role in priming immunotherapy responses. This first-in-human study highlights exosome-based precision therapy as a promising strategy against pancreatic cancer.
Targeting Protein Damage Response to Beat Cancer Drug Resistance
Journal: Cell Discov 11, 80 (2025).
Author: Shao, F., Li, Z., Xiao, H. et al., China
Researchers have identified a new mechanism behind multidrug resistance in cancer: the Protein Damage Response (PDR). Many anticancer drugs inadvertently damage newly made proteins – especially in mitochondria – triggering a protective repair process driven by proteasome activity. Patients with advanced breast and colon cancers often show elevated proteasome activity, making them resistant to therapy. A new diagnostic kit can detect this activity to guide treatment, while clinical studies show that FDA-approved proteasome inhibitors can overcome resistance and restore drug sensitivity.
ADAR Variants Linked to Gut Inflammation
Journal: Nat Commun 16, 8560 (2025).
Author: Xu, P., Xi, Y., Kim, JW. et al., USA/ China/ Republic of Korea
A new study reveals that loss-of-function in the RNA-editing enzyme ADAR disrupts intestinal homeostasis and drives inflammatory bowel disease (IBD). Researchers found reduced ADAR expression in patient intestinal tissue, while ADAR inhibition in mice triggered spontaneous colitis. Organoid models showed that ADAR loss causes double-stranded RNA and endogenous retrovirus buildup, activating immune signaling through MDA5 and the JAK/STAT pathway. A human ADAR mutation (p.N173S) failed to prevent disease, but treatment with the JAK inhibitor Ruxolitinib alleviated symptoms. These findings highlight the ADAR–MDA5–JAK/STAT axis as a promising therapeutic target for IBD.
