To address these challenges, we develop a liposomal nanodrug that co-encapsulates a mitochondrial-targeted photosensitizer (MP) and a TGF-β receptor inhibitor (LY2109761) to synergize PDT with PD-1 checkpoint blockade...In murine PDAC models, this dual-action strategy transforms the immune-cold TME into an immune-inflamed phenotype, sensitizing tumors to PD-1 therapy and leading to pronounced tumor regression and prolonged survival. Our findings present a promising nanodrug-based approach to remodel the fibrotic and immunosuppressive TME of PDAC and enhance immunotherapeutic outcomes.

P1, N=30, Completed, Agomab Spain S.L.U. | Trial completion date: Dec 2025 --> Sep 2025 | Trial primary completion date: Dec 2025 --> Sep 2025 | Recruiting --> Completed

While these findings highlight a synergistic anti-MASH effect of THU and EW-7197, the study is positioned as proof-of-concept. Further validation in metabolically relevant models (e.g., HFD/HFHC) and pharmacokinetic analyses are warranted before clinical translation can be considered.

CD44 was knocked down in claudin‑low breast cancer cell lines (SUM159 and MDA‑MB‑231), and the TGF‑β receptor (TGFBR) inhibitor LY2109761 (LY‑61) was applied for treatment...Although CD44 depletion may increase EMT‑related signaling, invasion was primarily suppressed by TGF‑β blockade, and the combination with CD44 knockdown further enhanced the inhibition of proliferative phenotypes compared with either treatment alone. This dual‑targeting approach warrants further investigation in claudin‑low breast cancer.

P1, N=223, Active, not recruiting, Eli Lilly and Company | Trial completion date: Aug 2025 --> Aug 2026

P2, N=65, Completed, Genfleet Therapeutics (Shanghai) Inc. | Active, not recruiting --> Completed

P1/2, N=0, Withdrawn, The Netherlands Cancer Institute | N=31 --> 0 | Unknown status --> Withdrawn

P1, N=40, Recruiting, Agomab Spain S.L. | Not yet recruiting --> Recruiting

The activation of the TGF-β/SMAD pathway and its interaction with the DNA repair via through ATR transductor was demonstrated. LY2109761 could act as a radiosensitizer for BNCT.

These hits exhibited lower free energies (ΔG) as compared to the benchmark inhibitors, Galunisertib and Vactosertib. The results offer valuable insights into the binding mechanism of protein TGFßR1 and its role in the disease, suggesting that targeting the TGF-ß signaling pathway may represent a promising therapeutic strategy.

P2, N=65, Active, not recruiting, Genfleet Therapeutics (Shanghai) Inc. | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: May 2025 --> Oct 2025

P1, N=40, Not yet recruiting, Agomab Spain S.L.