P1/2, N=39, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Apr 2029 --> Jul 2029 | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Apr 2029 --> Jul 2029

Furthermore, VP exhibited inhibitory effects on TGF-β-induced epithelial-mesenchymal transition and cell migration. Our findings indicate a novel approach to develop protein-protein interaction inhibitors of the canonical TGF-β signaling pathway for treatments of related diseases.

Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

P2, N=25, Not yet recruiting, Mayo Clinic

P2, N=42, Recruiting, Soligenix | Trial completion date: Dec 2023 --> Jun 2025 | Trial primary completion date: Oct 2023 --> Apr 2025

Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects...Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required.

Furthermore, it could effectively improve the survival rate in the rat model of K. pneumonia-induced pneumonia and ameliorate histological changes while protecting the integrity of the pulmonary epithelial cells. These results highlight the potential application of LD4 as a photosensitizer for treating acute pneumonia induced by K. pneumoniae.

Our findings emphasize that BG has the potential to be used as a protective natural remedy for human PTC cells.

SG can enhance hepatic regenerative capacity and improve liver metabolism. This study provides a better understanding of the mechanisms underlying SG-induced metabolic improvements.

Therefore, we propose that intracellular localization of GSK3β could be a good marker of response to PDT in HNSCC. Although the molecular mechanism of response to PDT needs further elucidation, this work shows that the most MAL-resistant line of CSCC is more sensitive to Temoporfin.

P1, N=12, Recruiting, Roswell Park Cancer Institute | Phase classification: P2 --> P1 | N=82 --> 12

Overall, the results of this preclinical study showed that HANP/VP is an effective nanomedicine for tumor treatment through PDT and inhibition of YAP in the UM tumor mouse model. Combining phototherapy and molecular-targeted therapy offers a promising approach for aggressive UM management.

P1, N=30, Recruiting, Nader Sanai | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

JCAD deficiency leads to an impaired liver growth after PH due to cell division blockage. JCAD competes with LATS2 for WWC1 interaction, resulting in LATS2 inhibition, YAP activation and enhanced expression of cell cycle-associated genes. Delineation of JCADHippoYAP signalling pathway would facilitate to improve prognosis of acute liver failure and graft growth in living-donor liver transplantation.

P4, N=0, Withdrawn, Wake Forest University Health Sciences | N=150 --> 0 | Suspended --> Withdrawn

Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts (p < 0.0001). This study demonstrates the efficacy of targeted fluorescence imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models.

Treatment with verteporfin inhibited YAP's binding to TEAD and reversed the elevated expression of AMPKα1 in the cells overexpressing CFP-YAP...In addition, the AMPKα1 puncta were demonstrated to inhibit cell viability, autophagy, and proliferation, and ultimately promote cell senescence. In conclusion, YAP binds to TEAD to upregulate AMPKα1 and promotes the formation of AMPKα1 puncta around mitochondria under the condition of co-expression of CFP-YAP and YFP-AMPKα1, in which AMPKα1 puncta lead to cellular senescence.

P3, N=100, Recruiting, Steba Biotech S.A. | Trial primary completion date: Feb 2024 --> Dec 2024

In this review, we summarize and discuss the approaches to overcome PDT obstacles by means of endogenous production of excitation light, photosensitizers, and oxygen. We envision that as synthetic biology advances, genetically engineered cells could act as precise and targeted "living factories" to produce PDT components, leading to enhanced performance of PDT.

P1/2, N=12, Recruiting, Kiora Pharmaceuticals, Inc. | Trial completion date: Mar 2024 --> Jan 2025 | Trial primary completion date: Feb 2024 --> Dec 2024

Simultaneous delivery of PS and ASO elicited synergistic apoptosis to an extent that could not be reached by singly loaded nanocarriers or the free form of the drugs. Both, the distinct location of loaded compounds that prevents them from interfering with each other, and the highly efficient cellular delivery support the great potential of this versatile peptide platform in combination therapy.

P1/2, N=39, Not yet recruiting, Roswell Park Cancer Institute

Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.

P1, N=36, Not yet recruiting, Impact Biotech Ltd | Trial completion date: Dec 2026 --> Dec 2027 | Initiation date: Oct 2023 --> May 2024 | Trial primary completion date: Mar 2025 --> May 2026

P1, N=30, Not yet recruiting, Impact Biotech Ltd | Trial completion date: Oct 2025 --> Oct 2026 | Initiation date: Oct 2023 --> Apr 2024 | Trial primary completion date: Oct 2024 --> Apr 2025

P1/2, N=24, Recruiting, Emory University | Trial primary completion date: Aug 2024 --> Aug 2025

P2, N=15, Not yet recruiting, Lawson Health Research Institute | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P=N/A, N=224, Completed, Galderma Laboratorium GmbH | Recruiting --> Completed | N=350 --> 224

P1, N=22, Active, not recruiting, Alpheus Medical, Inc. | Recruiting --> Active, not recruiting | N=48 --> 22 | Trial completion date: Dec 2024 --> Apr 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P3, N=186, Active, not recruiting, Biofrontera Bioscience GmbH | Trial primary completion date: Dec 2023 --> Mar 2024

P2, N=126, Recruiting, Biofrontera Bioscience GmbH | Trial completion date: Mar 2024 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Feb 2025

P1, N=12, Recruiting, Immunolight, LLC | Trial completion date: Feb 2025 --> Aug 2025 | Trial primary completion date: Mar 2024 --> Sep 2024

P2, N=40, Recruiting, SonALAsense, Inc. | Phase classification: P1/2 --> P2

P1/2, N=8, Active, not recruiting, SonALAsense, Inc. | Recruiting --> Active, not recruiting | N=44 --> 8

P2, N=15, Recruiting, Kintara Therapeutics, Inc. | Not yet recruiting --> Recruiting | Trial primary completion date: Sep 2024 --> Dec 2024

In vitro and in vivo studies showed that CPPa NP can successfully elevate the ROS level within 4T1 cells and has a better anticancer efficacy than PPa NP without CI-994 under laser irradiation. This study thus provides an effective approach to develop self-amplified activatable nanoparticles for enhanced PDT.

Furthermore, Verteporfin (a small molecule inhibitor of YAP) interrupted the YAP-TEAD interaction and inhibited FAK phosphorylation, confirming that YAP can induce FAK phosphorylation in a TEAD-dependent manner...Silencing HMGB1 reversed YAP-induced FAK activation as well as cell proliferation and migration. Collectively, our results reveal a new signalling axis, YAP/HMGB1/FAK, in the regulation of cell proliferation and migration, and provide new insights into the crosstalk between Hippo signalling and cell proliferation.

P3, N=165, Recruiting, Biofrontera Bioscience GmbH | Active, not recruiting --> Recruiting

LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function; thus, VP, which targets this axis, may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

Verteporfin was identified as a more selective and potent antagonist than the known CCR5 antagonist maraviroc. Overall, this study introduced an easy-to-use HTS assay that streamlines the discovery of CCL5/CCR5 axis antagonists. Verteporfin was identified as a specific molecular probe of this axis with great potentials as a therapeutic agent for treating sixteen malignant diseases characterized by heightened CCR5 and YAP1 levels.

Temoporfin, another photodynamic drug, did not show similar activities...Notably, the activity of VP to induce lipid peroxidation was neutralized by ferroptosis inhibitors ferrostatin-1 or liproxstatin-1...These results indicate that VP can induce lipid peroxidation and ferroptosis in the absence of light activation. Our findings reveal a novel mechanism by which VP inhibits tumor growth and provide insights into development of new therapeutic strategies for the treatment of pancreatic cancer.

P2, N=82, Recruiting, Roswell Park Cancer Institute | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024