Remarkably, the TGF-β inhibitor LY2157299 effectively countered TGF-β activity and significantly reversed tumor metastasis and EMT induced by CLIP170 knockdown. In summary, these findings collectively propose CLIP170 as a promising therapeutic target to mitigate metastatic tendencies in PTC.

Additionally, miR-431-5p enhances the efficacy of anti-PD1 treatment, particularly when combined with galunisertib, anti-PD1 treatment showing a synergistic effect in inhibiting GC progression in C57BL/6 mice. Collectively, these findings suggest that miR-431-5p may modulate the TGF-β1/SMAD2/3 pathways by targeting ZEB1 to impede GC progression, angiogenesis, and lymphangiogenesis, making it a promising therapeutic target for GC management.

P2, N=300, Recruiting, Avalyn Pharma Inc. | Not yet recruiting --> Recruiting | N=230 --> 300

P1, N=362, Recruiting, AbbVie | Trial primary completion date: Feb 2026 --> Jun 2027

P2, N=58, Completed, Scholar Rock, Inc. | Active, not recruiting --> Completed

Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells...In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.

P2, N=140, Recruiting, EpicentRx, Inc. | Trial completion date: Mar 2025 --> Mar 2027 | Trial primary completion date: Mar 2024 --> Dec 2025

P2, N=230, Not yet recruiting, Avalyn Pharma Inc.

Further, TQ significantly attenuated liver fibrosis, as illustrated by the downregulation of TAA-induced interleukin-β, tumour necrosis factor-α, inducible nitric oxide synthase and fibrosis markers like transforming growth factor-β (TGF-β), α-smooth muscle actin, collagen-1, Smad3 and 7. Therefore, these findings suggest that TQ has a promising hepatoprotective property, as indicated by its potential to effectively suppress TAA-induced liver fibrosis in rats by inhibiting oxidative stress and inflammation via TGF-β/Smad signaling.

P2/3, N=840, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P2, N=44, Completed, Sirnaomics | Active, not recruiting --> Completed | N=100 --> 44

P1, N=20, Completed, Sirnaomics | Active, not recruiting --> Completed | N=50 --> 20

P1, N=8, Completed, Sirnaomics | Active, not recruiting --> Completed

P1, N=5, Completed, Sirnaomics | Active, not recruiting --> Completed | N=50 --> 5

P1, N=50, Active, not recruiting, Sirnaomics | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Mar 2024 | Trial primary completion date: Sep 2024 --> Mar 2024

P1/2, N=9, Completed, Sirnaomics | Active, not recruiting --> Completed | N=30 --> 9 | Trial completion date: Jul 2023 --> Mar 2023 | Trial primary completion date: Jul 2023 --> Mar 2023

P2, N=32, Completed, Sirnaomics | Active, not recruiting --> Completed | N=15 --> 32

P2, N=29, Completed, Sirnaomics | Active, not recruiting --> Completed | N=60 --> 29

P1, N=337, Recruiting, AbbVie | Trial completion date: Feb 2026 --> Jun 2027

P2, N=205, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: May 2024 --> Sep 2024

P1, N=18, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | Trial completion date: Jan 2027 --> Feb 2026 | Trial primary completion date: Jan 2027 --> Feb 2025

Mechanically, PHI inhibited TGF-β1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/β-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.

P1/2, N=60, Active, not recruiting, HCW Biologics | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2

P2, N=140, Recruiting, EpicentRx, Inc. | Phase classification: P1/2 --> P2 | N=79 --> 140

P2/3, N=840, Not yet recruiting, AbbVie

Based on these findings, we designed nanogels that have two primary characteristics: (1) they encapsulate galunisertib (Gal), which is used clinically to inhibit TGF-β receptor activity, thereby blocking TGF-β signaling; and (2) they provide cells with a surface coating of 25 K bPEI...These findings suggest that Gal-loaded 25 K bPEI-coated nanogels exert anti-tumor effects via chemical priming, as well suppressing the effects of TGF-β on NK cells. We also expect 25 K bPEI-based nanogels to have great potential to overcome the suppressive effects of the TME through their NK cell-priming activity and delivery of the desired chemicals.

Our findings suggest that dual-targeted immunotherapy may have a superior antitumor effect. Our study presents a technique to evolve novel, robust, timely therapeutic strategies and interventions for EC and other malignancies.

Effects of constant activation of the SMAD pathway by constitutive expression of ALK5 or knockdown of mediators of TLR signalling, IRAK1 and MyD88, on HCC proliferation, were investigated in the HCC cell line (HUH-7) after treatment with TGFβ1 cytokine or TGFβR1 kinase inhibitor (LY2157299) using PCNA and MTS assay...There is a balance between the canonical SMAD-driven tumour-suppressing arm and the non-canonical tumour-promoting arm of TGFβ signalling. Disruption of this balance, by inhibition of the canonical pathway, induces HCC proliferation through TLR signalling.

Neural involvement enhanced tumor aggressiveness through upregulating TGFβ signaling and PD-L1 expression in OSCC, while denervation of OSCC inhibited tumor growth, down-regulated TGFβ signaling, enhanced activities of CD8+ T cells and improved the efficacy of anti-PD-1 immunotherapy. This study will encourage further research focusing on denervation as a potential adjuvant therapeutic approach in OSCC.

P1, N=64, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Jun 2024 --> Jan 2024

In this study, we developed an oral microgel delivery system of EcN@(CS-SA) by electrostatic interaction between chitosan (CS) and sodium alginate (SA), aiming to enhance its bioavailability in the gastrointestinal tract (GIT). Notably, EcN@(CS-SA) microgel showed a synergistic enhancement of the anti-tumor efficacy of Galunisertib (Gal, a TGF-β inhibitor) by inducing apoptosis and immunogenic cell death (ICD) in tumor cells, as well as promoting increased infiltration of CD8 T cells into the tumor microenvironment (TME).

P1, N=64, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=112, Active, not recruiting, Scholar Rock, Inc. | Recruiting --> Active, not recruiting | N=74 --> 112 | Trial primary completion date: Dec 2023 --> Dec 2024

P1; N=29; Completed; Sponsor:Vanderbilt-Ingram Cancer Center

P3, N=511, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2026 --> Jun 2024 | Trial primary completion date: Jan 2026 --> Jun 2024

To elucidate the underlying mechanism, we compared the efficacy of PFD after pretreatment with either TGF-β1 or a TGF-β receptor inhibitor (LY2109761). Additionally, PFD combined with cisplatin targeted TGF-β1 to inhibit glycolysis during EMT and enhanced the chemosensitization of A549 and H1299 cells. The magnitude of the anticancer effect exhibited by PFD was intricately linked to its metabolic properties.

P2/3, N=660, Recruiting, AbbVie | Not yet recruiting --> Recruiting | Phase classification: P2 --> P2/3

Vigil is an autologous cellular immunotherapy which is designed to carry the full set of personal clonal neoantigens. Phase 2b results demonstrate a durable recurrence-free survival (RFS) and overall survival (OS) advantage for Vigil in a subset ovarian cancer population with an HRP cancer profile.

P2, N=180, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2023 --> Sep 2024

P4, N=60, Recruiting, The First Affiliated Hospital of University of science and technology of China (Anhui Provincial Hospital); The First Affiliated Hospital of Universit | Phase classification: P3 --> P4

In patients with advanced solid tumors, proof of mechanism of NIS793 is supported by evidence of target engagement and TGF-β pathway inhibition.

P1, N=35, Completed, Seoul National University Hospital | Recruiting --> Completed