However, as an inhibitor of this pathway, LY2109761 could reverse the effects induced by GOLPH3 overexpression. Collectively, these findings establish GOLPH3 as a critical driver of PTC malignancy through TGF-β pathway activation, providing a mechanistic link between Golgi function and cancer signaling. This work not only advances our understanding of PTC pathogenesis but also identifies GOLPH3 as a potential therapeutic target for aggressive PTC, offering a paradigm for exploring Golgi-associated proteins in endocrine malignancies.

Similar re-sensitizing effects of mitoxantrone were also observed in colony formation and multicellular tumor spheroid assays. In addition to functional inhibition, vactosertib reduced the expression levels in both ABCG2 mRNA and protein without altering membrane localization, suggesting transcriptional downregulation. As a result, these findings indicate that vactosertib reverses ABCG2-mediated MDR through dual effects on inhibiting ABCG2 function and downregulating and the expression of ABCG2, supporting its potency as a chemo sensitizing agent in ABCG2-mediated MDR cancer models.

SB-525334 blocked all effects of TGF-β1, whereas nintedanib was more effective in counteracting the stimulatory effects of TGF-β1 on cell length and α-SMA. Interestingly, nintedanib, per se, evoked small but consistent effects opposite to those of TGF-β1. In conclusion, integrating these experimental approaches provides a powerful platform for detailed investigation of EMT mechanisms and for the identification of novel drug candidates that counteract EMT.

Both LY3200882 and THZ1 affected the NK cell transcription even without cytokine treatment. The independent effects of synthetic inhibitors on NK cells, as well as their influence in the presence of tumor cells, should be considered.

P1, N=223, Active, not recruiting, Eli Lilly and Company | Trial completion date: Aug 2026 --> Aug 2027

We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation.

To address this, an intelligent and injectable thermo-responsive hydrogel delivery system (LY@CNSG) constructed from cyclodextrin nanosponges and poly(N-isopropylacrylamide) was developed, in response to immunosuppressive prostaglandin E2 (PGE2) levels for autonomously controlling the release of LY2109761 (LY, a TGF-β inhibitor) based on competitive host-guest interaction. In triple-negative breast cancer models, photodynamic therapy combined with LY@CNSG significantly inhibited tumor growth and lung metastasis while enhancing antitumor immune activity. Furthermore, by integrating nitric oxide (NO)-responsive fluorescent probes, we created an integrated hydrogel platform, CYNH2-LY@CNSG, for simultaneous immunomodulator delivery and immune signaling molecule monitoring, providing a novel insight for biomarker monitoring and a more precise immunotherapy paradigm.

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.

P1, N=145, Recruiting, Agomab Spain S.L. | N=107 --> 145 | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

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.