The TGFβRI inhibitor LY2157299 attenuates fibrosis in vivo. Strikingly, PT637 disrupts the Spata13-TGFβRI interaction and reduces both fibrosis markers and capsular thickness in biofilm-challenged rats. We define Spata13 as a novel regulator of infection-associated fibrosis and demonstrate that targeted disruption of Spata13-TGFβRI binding by PT637 offers a precision therapeutic strategy for capsular contracture.

Herein, we report a chemoimmunotherapeutic fibrin sealant (CI-sealant) as a new postsurgical adjuvant therapy that converts the surgical cavity into an in situ "drug-immune depot" with localized release of immunogenic docetaxel/volasertib dual-drug nanocombo (iNCombo) and galunisertib, a TGF-β inhibitor that relieves immune suppression. Post-surgery adjuvant therapy with CI-sealant significantly prevents tumor recurrence in both murine 4 T1-Luc breast tumor and B16F10 melanoma models. This chemoimmunotherapeutic sealant opens a promising strategy for postsurgical adjuvant therapy of malignant tumors.

P2, N=100, Completed, Avalyn Pharma Pty Ltd | Active, not recruiting --> Completed

2-Deoxy-D-glucose (2DG), a glycolytic inhibitor, depleted ATP dose-dependently (30-300 μM) and prevented those increases both at the protein and transcriptional levels. This was also observed in 3D spheroids upon TGF-β transient siRNA-mediated silencing or when TGF-βR1 kinase activity was inhibited by galunisertib...3D spheroids require ATP and a TGF-β/TGF-βR1 autocrine signaling axis to recapitulate the apoptosis/autophagy phenotypes. Combining glycolysis inhibition with TGF-β signaling inhibition could offer a promising therapeutic strategy for this rare and lethal brain cancer.

P2, N=50, Active, not recruiting, Providence Health & Services | Trial completion date: Dec 2025 --> Dec 2026

In the randomized phase II H9H-MC-JBAJ trial, high baseline ANG predicted poor survival with gemcitabine alone but significant benefit from galunisertib addition. Clinically, elevated ANG correlated with systemic TNF-α, and galunisertib reduced TNF-α exclusively in ANG-high patients, with reductions associated with markedly improved survival. These findings define an ANG-EGFR-TGFβ-TNF-α axis in TAMs as a stromal driver of PDAC chemoresistance, and provide a mechanistic rationale for the development of combination strategies targeting ALK5 signaling in ANG-high PDAC patients.

In vivo in orthotopic tumors formed by FC1199 cells GAL decreased CD9+-NK frequency, promoted M1-macrophage polarization, and activated NK and CD8+T-cells, together with a significant reduction of tumor weight, fibrosis and inhibition of angiogenesis. Our study identifies CD9+NKs as a novel cell subset expanded in PDAC and underscores the role of TGF-β1/TGF-βR1 signalling in promoting a pro-tumoral NKs GAL-treatment emerges as immunomodulator able in re-educating pro-tumor NKs cells in PDAC.

To model acquired resistance, we established two mTORi-resistant TNBC cell lines, MDA-MB-231/DREVE and MDA-MB-231/DRRIDA through chronic exposure to everolimus and ridaforolimus, respectively...Pharmacological inhibition of upstream TGF-β signaling with galunisertib suppressed PMEPA1 and synergistically restored sensitivity to mTORi in both invitro and xenograft models, resulting insignificant tumor regression...Collectively, these findings establish PMEPA1 as a dual modulator of canonical and non-canonical TGF-β signaling and a critical mediator of mTORi resistance in TNBC. Targeting the TGF-β/PMEPA1 axis represents a promising strategy to overcome resistance and improve clinical outcomes in mTORi-refractory TNBC.

P2, N=60, Not yet recruiting, Scholar Rock, Inc.

P2/3, N=840, Recruiting, AbbVie | Active, not recruiting --> Recruiting | N=167 --> 840

P1/2, N=121, Recruiting, Avalyn Pharma Inc.

P1/2, N=30, Recruiting, Scholar Rock Inc.