The MBRG-based model effectively predicts BLCA prognosis, integrates mechanisms of basement membrane remodeling, EMT, and immune suppression, and identifies DDR2 and SERPINF1 in CAFs as potential targets for personalized therapy.

P2, N=36, Recruiting, The First Affiliated Hospital of Zhengzhou University

The interactions within tumor microenvironment were involved disease progression. Overall, first-line SHR-1701 plus AG showed promising anti-tumor activity and controllable safety in advanced or metastatic pancreatic ductal adenocarcinoma, and features of patients more likely to benefit from the combination were drawn.

P3, N=700, Not yet recruiting, Incyte Corporation

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.

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.

Patients received concurrent SHR-1701 and CRT, followed by two cycles of SHR-1701 plus XELOX and subsequent TME surgery. One patient experienced fatal immune-mediated myocarditis prior to surgery. Overall, the addition of SHR-1701 to CRT demonstrated encouraging efficacy and manageable safety in high-risk LARC, supporting further investigation in larger randomized trials.

P2, N=36, Not yet recruiting, Fudan University

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.

P=N/A, N=42, Recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University | Not yet recruiting --> Recruiting

Human LUAD cells HCC827 and H1975 were exposed to different doses of osimertinib or erlotinib to generate TKI-resistant cell lines. Notably, the LY2109761 treatment reduced TKI resistance and diminished expansion, migration, and stemness in cancer cells induced by EMP3 overexpression. In conclusion, this study indicates that EMP3, upregulated upon EMT, contributes to EGFR-TKI resistance in LUAD cells.

The present research was designed to explore the impact of TGF-β1 inhibitors (LY2109761 and LY3200882) with or without gemcitabine on bladder cancer cells and to develop Pluronic F-127-based microspheres (MSs) for drug delivery. Systemic and local bladder toxicity assessments in mice demonstrated the in vivo safety of drug-loaded MSs. This study concludes that combining TGF-β1 inhibitors with gemcitabine in Pluronic F-127-based MSs enhances therapeutic efficacy against bladder cancer, promoting apoptosis, inhibiting cell invasion, and reducing tumor growth and metastasis while maintaining safety.