To counteract this resistance mechanism, we developed a TME-responsive nanogel (pirfenidone@nanogel-hyaluronidase-anti-PD-L1 [PFD@NGHP]) for rescuing radiosensitization...This effect synergized radiotherapy to sustain tumor regression and generate abscopal effects. Collectively, our study demonstrates that PFD@NGHP targets the TGF-β1-PD-L1 axis in a cascading manner, offering a promising clinical strategy to overcome the adaptive radioresistance of irradiated pancreatic ductal adenocarcinoma while providing a potential platform for translational nanomedicine evaluation.

P2, N=20, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1/2, N=135, Recruiting, Akeso | Not yet recruiting --> Recruiting

P2, N=160, Recruiting, Akeso | Not yet recruiting --> Recruiting

Standard-of-care treatments (pirfenidone, nintedanib) reduced FUS expression in PCLs. In contrast, ION363 promoted functional marker expression and improved morphology in patient-derived 3D alveolospheres. We conclude that FUS is a pivotal regulator of fibrotic signaling in IPF and that targeting FUS via ASO represents a promising therapeutic avenue for IPF.

P=N/A, N=200, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting | Initiation date: Oct 2025 --> Feb 2026

P3, N=300, Not yet recruiting, Takeda

P2/3, N=191, Recruiting, Bicara Therapeutics Inc.

P2/3, N=389, Recruiting, Merck Sharp & Dohme LLC

P=N/A, N=418, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Mar 2025

Early diagnosis of acute promyelocytic leukemia (APL), driven by PML-RARA oncoprotein, is vital for survival, as delays can cause fatal coagulopathy without prompt therapeutic intervention of all-trans retinoic acid and arsenic trioxide...Pharmacological inhibition of TGF-β1 ligand using luspatercept reduced SMAD phosphorylation and PDPN expression, indicating TGF-β/SMAD transcriptionally regulates PDPN. Additionally, ELISA-based serum profiling showed significantly elevated TGF-β1 levels in APL patients compared to non-APL AML (p < 0.0001). These findings identify PDPN overexpression as a downstream consequence of TGF-β/SMAD signaling and highlight its potential as a diagnostic biomarker for APL.

In this report, the complex mechanism of luspatercept is discussed with a literature review on the clinical trials leading to its approval in MDS patients. Furthermore, we connect the pathophysiology between the formation of this patient's telangiectasias leading to her PAVM with the disruption of the TGF-β/SMAD pathway from luspatercept use.