Visudyne (verteporfin)

The significantly differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) database, which discriminate AGS and MKN45 cells in the presence of DMSO and verteporfin (a chemotherapy reagent), are determined...MKN45 was highlighted as more invasive cancer cell relative to AGS cells. PLOD2 was pointed out as a suitable target in the chemotherapy of gastric cancer.

This study identified a novel CAF-exosome-YAP-USP8-HER2 signaling axis that drives trastuzumab insensitivity in HER2-positive breast cancer. Intervening in this pathway may represent a potential treatment approach to counteract microenvironment-induced chemoresistance.

P1/2, N=12, Not yet recruiting, Odense University Hospital

In an immune-cold syngeneic mouse PDAC model, 690 nm light activation of SM-102-containing liposomes slowed tumor growth by up to 56% and extended survival by 40%. Together, these findings suggest that integrating SM-102 into light-activated liposomes is a simple and robust strategy to enhance photochemical ICD and may improve therapeutic outcomes in immunotherapy-based combinations that utilize liposomal drug delivery systems.

P1/2, N=66, Recruiting, SpectraCure AB | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Jul 2027

Targeted and molecular therapies in EWS show significant promise, particularly in rational combinations that exploit the tumor's dependence on EWS-FLI1-driven transcriptional dysregulation, DNA damage repair deficiencies, or survival signaling. Future research must prioritize biomarker-driven patient selection, integration of multiomics approaches, and multicenter prospective trials to translate these strategies into clinically meaningful improvements in EWS survival.

Knockdown of ZNF143/SAV1 signaling impaired the therapeutic effect of HWM, and treatment with verteporfin, pharmacological inhibition of YAP/TAZ, reversed the effects of knockdown of SAV1. Therefore, HWM might offer a potent strategy for managing TNBC effectively.

P2, N=12, Not yet recruiting, Odense University Hospital

To mitigate the off-target toxicity of verteporfin, a YAP1 inhibitor, we develop macrophage-membrane-camouflaged hollow mesoporous silica nanoparticles (M@O-VNPs) co-loaded with verteporfin and oxaliplatin...By inducing immunogenic cell death, M@O-VNPs remodel the tumor microenvironment and enhance ICB efficacy while minimizing systemic toxicity. The therapeutic potential of this strategy is supported by synergistic antitumor effects of M@O-VNPs combined with anti-PD-1 therapy in genetically engineered and syngeneic GC models.

To overcome this, we screened various metalloporphyrins and identified Cu-based verteporfin as an effective YAP inhibitor, so that a tumor-targeted nanosystem termed CuVP-F127-IKE-Mem is developed, which integrates the YAP inhibitor copper-verteporfin metalloporphyrin and the ferroptosis inducer imidazole ketone erastin (IKE) into cancer cell membrane-coated nanoparticles. In pancreatic cancer, CuVP-F127-IKE-Mem significantly enhances ferroptosis sensitivity, suppresses YAP/SLC7A11 signaling, and exhibits potent tumor growth inhibition in vivo. This YAP-targeted transcriptional regulation strategy establishes a new paradigm for overcoming ferroptosis resistance.

In this study, we designed and synthesized Photodegradation-Targeting Chimeras (PDTACs) by conjugating a clinically approved photosensitizer, verteporfin, to a PD-L1-targeted peptide...In mouse models with immune cold tumors, PPA-VPF elicited robust adaptive antitumor immunity and effectively inhibited the growth of both primary and distant tumors. This PD-L1-targeted PDTAC achieved immune checkpoint blockade and ICD induction in a single therapeutic mode using one molecular species, presenting a novel strategy for combinational immunotherapy, particularly in immune cold tumors.

YAP1 and tumor-like CAFs (tCAFs) play a pivotal role in driving desmoplasia in PDAC. YAP1 mediates the conversion of mCAFs to tCAFs and remodels the extracellular matrix (ECM), while high YAP1 activity in tCAFs regulates EMT induction to propel disease progression. Targeting the YAP1-tCAF axis can suppress desmoplasia and improve therapeutic outcomes. Magnetic resonance elastography (MRE) holds significant potential for non-invasive monitoring of stromal mechanics, offering a new perspective for stromal therapies in PDAC.