Visudyne (verteporfin) / Novartis, Bausch Health - LARVOL DELTA

Non-Syndromic Hereditary Gingival Fibromatosis Driven by Chymase Deficiency Is Attenuated by Verteporfin-Loaded Exosomes. (PubMed, J Clin Periodontol) - "Our findings support the pathogenic role of the CHYMASE mutation in nsHGF, establish chymase deficiency and consequent YAP/TAZ activation as the underlying mechanism and propose verteporfin-loaded exosomes as a promising therapeutic strategy for nsHGF-associated gingival overgrowth."

Journal • Dental Disorders • Fibrosis • Immunology • Periodontitis • Solid Tumor • IL6

Combination of YAP inhibition and photodynamic therapy induces dual DNA damage and activates STING pathway to enhance immunotherapy in uveal melanoma. (PubMed, Redox Biol) - "This approach, using hyaluronic acid nanoparticle (HANP)-formulated verteporfin (HANP/VP), concurrently induced nuclear- and mitochondrial-DNA damage, promoted immunogenic cell death (ICD), and drove T-lymphocyte infiltration into the tumor microenvironment (TME)...Overall, our findings established HANP/VP as a multifunctional nanomedicine that reprogrammed the TME and elicited potent antitumor immunity through dual DNA damage and STING activation. The study highlights a promising translational strategy for overcoming immunotherapeutic resistance in UM and converting immunologically "cold" tumors into "hot" ones, thereby improving responses to immune checkpoint blockade (ICB)."

Journal • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD8 • IFNB1 • IFNG • STING • TNFA

Hypoxic Tumor Microenvironment Promotes Hippo Pathway Transcriptional Activity to Enrich Glioma Stem Cells in the Peri-necrotic Niche of Glioblastoma (SNO 2025) - "AKT inhibition with Capivasertib reduced Zyx phosphorylation and Hippo transcription in hypoxia...Blocking TGFBR2 with inhibitor LY2109761 abolished TGF-β1-induced Hippo activation...In vivo, pharmacologic inhibition of YAP/TAZ with Verteporfin or genetic TAZ knockdown in the RCAS/tv-a mouse model reduced tumor burden and prolonged survival. Flow cytometry confirmed decreased CD133+/CD44+ GSCs in TAZ-deficient tumors. These results demonstrate hypoxia and TGF-β1 signaling to activate YAP/TAZ-driven Hippo signaling, promoting GSC maintenance in the peri-necrotic GBM niche."

Biomarker • Tumor microenvironment • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CCN1 • CD133 • FOXM1 • OLIG2 • SOX2 • TAFAZZIN • TGFB1 • TGFBR2 • YAP1

Eriocitrin inhibits sodium iodate-induced cuproptosis and barrier function impairment in retinal pigment epithelium via SIRT7/YAP/ATP7A pathway. (PubMed, J Transl Med) - "This study demonstrated that eriocitrin alleviates NaIO₃-induced oxidative stress and RPE barrier dysfunction by modulating the SIRT7/YAP/ATP7A signaling pathway and inhibiting cuproptosis. Our findings indicated eriocitrin as a promising natural therapeutic candidate for dry AMD and lay the foundation for developing flavonoid-based anti-cuproptosis strategies."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • ATP7A • SIRT7

Silibinin inhibits F-actin assembly leading to G2/M cell cycle arrest in human breast cancer cells - is targeted therapy on the horizon? (PubMed, Biochem Pharmacol) - "Our results reveal the F-actin assembly is inhibited by silibinin, and this results in G2/M cell cycle arrest in human breast cancer cells, providing new ideas for anti-cancer therapies including TNBCs. Abbreviations: ABPs, actin binding proteins; ARP2, actin-related protein2; Capza1, capping actin protein of muscle Z-line subunit alpha 1; CDC2, Cell Division Cycle protein 2/CDK1, Cyclin-Dependent Kinase 1; CDKi, cyclin-dependent kinase inhibitors; CDKs, cyclin-dependent kinases; CETSA, cellular thermal shift assay; CFL1, cofilin 1; Cyto D, Cytochalasin D; DARTS, drug affinity responsive target stability; DIAPH3, diaphanous related formin 3; DMEM, Dulbecco's Modified Eagle medium; ER, estrogen receptor; F-actin, filamentous actin; FBS, fetal bovine serum; G-actin, globular actin; GSN, gelsolin; HER2, human epidermal growth factor receptor 2; LAMP1, lysosomal associated membrane protein 1; NLS, nuclear localization signal; PDB, protein data bank; PFN1, profilin 1; PR,..."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ACTR2 • CDK1 • DIAPH3 • ER • GSN • HER-2 • LAMP1 • PGR

FAM189A2 activates Hippo signaling pathway by abrogating WWP2-mediated LATS1 ubiquitination, to inhibit the glycolysis and proliferation processes of lung adenocarcinoma. (PubMed, J Transl Med) - "FAM189A2 can be considered as a potential diagnostic and prognostic marker associated with LUAD, and suppresses the proliferation and glycolytic metabolism of LUAD cells via WWP2-LATS1-YAP signaling, which will provide a corresponding theoretical foundation for the development of small molecule inhibitors."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Transplantation • LATS1 • WWP2

Quercetin alleviates rifampicin-induced hepatocyte injury by modulating the Hippo-YAP signaling pathway. (PubMed, Front Med (Lausanne)) - "To investigate the protective effects of Quercetin, an antioxidant and anti-apoptotic flavonoid, against rifampicin (RFP)-induced hepatocyte injury via the Hippo-YAP signaling pathway. The protective effects were partially attenuated by Verteporfin, indicating Hippo-YAP pathway involvement. Quercetin alleviates RFP-induced hepatocyte injury by suppressing Hippo pathway kinases MST1 and LATS1, reducing YAP phosphorylation, and enhancing YAP nuclear translocation, thereby improving MMP and inhibiting apoptosis."

IO biomarker • Journal • Hepatology • Liver Failure • ANXA5 • BAX • BCL2 • CASP3 • LATS1

Dose threshold values for endovascular photodynamic therapy (PDT) in normal pig pancreas and human pancreatic cancer. (PubMed, Photochem Photobiol Sci) - "These findings suggest that PDT can potentially create a margin around major pancreatic blood vessels free of viable tumour tissue. The calculated dosimetry supports the feasibility of clinical application using the proposed Verteporfin dose and light delivery parameters, warranting further investigation in Clinical trials."

Journal • Oncology • Pancreatic Cancer • Solid Tumor

NF2/Merlin loss induces upregulation of an alternative Wnt5a/b signaling pathway sensitive to YAP inhibition (SNO 2025) - "In primary NF2-mutant meningioma lines, targeting this pathway via blocking Wnt secretion with the inhibitor LGK974 or YAP signaling with verteporfin, which is FDA approved, results in decreased cell viability and proliferation in vitro. These results indicate activation of the Wnt5a/b-YAP/TAZ alternative signaling pathway in NF2-mutant meningeal and Schwann cells, and a potential therapeutic effect of blocking this pathway in NF2-mutant meningiomas with a previously-FDA approved inhibitor. Additional research is needed on the receptors and molecular mediators playing a role in this pathway and how these drugs may have therapeutic benefits in vivo"

Alzheimer's Disease • Ataxia • Brain Cancer • CNS Disorders • Cognitive Disorders • Meningioma • Movement Disorders • Otorhinolaryngology • Solid Tumor • Ventriculomegaly • CTNNB1 • NF2

Synergistic Effects of HDAC Inhibition and Hippo Signaling Pathway Regulation in Glioblastoma (SNO 2025) - "In this study, we evaluated the therapeutic impact of combining the HDAC inhibitor SAHA (suberoylanilide hydroxamic acid) with Verteporfin, a Hippo signaling pathway regulator, in patient-derived GBM tumor spheres (TS13-64 and TS15-88). Our findings suggest that combined modulation of HDAC activity and Hippo pathway signaling represents a promising therapeutic strategy for GBM. This dual-targeted approach may overcome current treatment resistance and improve clinical outcomes in GBM patients."

Brain Cancer • Glioblastoma • Solid Tumor

Angiotensin II Activates Yes-Associated Protein (YAP) in Fibroblast Promoting Deep Fascia Remodeling. (PubMed, Int J Mol Sci) - "This gene expression was decreased by pretreatment with the AT1R antagonist irbesartan or the YAP inhibitor verteporfin. These findings show that Ang II acts as both a biochemical and biomechanical signal in the deep fascia, activating YAP signaling and promoting fibrotic remodeling. Our results uncover a new Ang II-YAP pathway in fascial fibroblasts, offering potential targets for therapy in fibrosis and related conditions involving the deep fascia."

Journal • Fibrosis • Immunology • Pain • COL1A1 • COL3A1

Theranostic Verteporfin-Conjugated Upconversion Nanoparticles for Cancer Treatment. (PubMed, Nanomaterials (Basel)) - "The synthesized core-shell upconversion nanoparticles (CS-UCNPs) were coated with new verteporfin (VP)-conjugated alendronate-terminated poly(N,N-dimethylacrylamide-co-2-aminoethyl acrylate) [Ale-P(DMA-AEA)] grafted with poly(ethylene glycol) (PEG). Under 980 nm NIR irradiation, CS-UCNP@Ale-P(DMA-AEA)-PEG-VP nanoparticles generated reactive oxygen species (ROS) due to the efficient energy transfer between CS-UCNPs and VP. In a pilot preclinical study, intratumoral administration of nanoparticle conjugates to mice, followed by exposure to NIR light, induced necrosis of pancreatic tumor and suppressed its growth."

Journal • Oncology • Pancreatic Cancer • Solid Tumor

Repeated exposure of anticancer agents to tumorspheres in open-surface microwell arrays for modeling chemotherapy-induced dormancy in colorectal cancer. (PubMed, Lab Chip) - "Following repeated exposure of an anticancer agent combination (5-fluorouracil/oxaliplatin/SN-38, FOLFIRINOX), tumorspheres were retrieved and subjected to various off-line assays...The agent verteporfin, which targets the signaling pathway associated with dormancy, exhibited improved efficacy (25.0-27.7%) in the elimination of dormant cells when administered in conjunction with FOLFIRINOX. This developed dormancy cancer model offers an efficient tool for dissecting the mechanisms of tumor dormancy and advancing the discovery of anticancer agents."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Melk facilitates pulmonary artery smooth muscle cell proliferation and migration in pulmonary hypertension via modulation of YAP/TAZ signaling. (PubMed, Front Cell Dev Biol) - "The YAP inhibitor Verteporfin blunted MELK-driven PASMC proliferation and migration, underscoring the central role of YAP/TAZ signaling. Finally, in vivo pharmacological inhibition of MELK by OTS167 markedly reduced right ventricular systolic pressure, hypertrophy, and pulmonary vascular remodeling in Su/H mice, confirming the therapeutic relevance of MELK targeting in PAH. Collectively, these findings identify MELK as a novel regulator of PASMC pathobiology in PAH and suggest that it may represent a potential therapeutic target."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • AMPK • BIRC5 • CCN1 • CCND1 • CTGF • MELK • PCNA

T-2 toxin exacerbates chondrocyte extracellular matrix degradation potentially through YAP/NLRP3/GSDMD-mediated pyroptosis. (PubMed, Int Immunopharmacol) - "Inhibition of YAP by verteporfin effectively suppressed NLRP3/GSDMD pathway activation and alleviated ECM degradation, whereas YAP overexpression further exacerbated pyroptosis and ECM damage. These findings indicate that YAP activation mediates chondrocyte pyroptosis and exacerbates ECM degradation, potentially through the NLRP3/GSDMD pathway, representing a key mechanism underlying T-2 toxin-induced cartilage injury and a potential therapeutic target."

Journal • IL18 • IL1B • NLRP3

Multifunctional nanoagonist enhances photodynamic therapy-driven in situ cancer vaccination by inhibiting tumor thrombosis. (PubMed, J Nanobiotechnology) - "cDVPMA was constructed by encapsulating the stimulator of interferon genes (STING) agonist 2'3'-cGAMP in the aqueous core of a tertiary ammonium group-containing polymersome, while embedding both the photosensitizer verteporfin-phospholipid (VL) and thrombin inhibitor dabigatran etexilate within the hydrophobic layer. In a 4T1 mouse breast cancer model, cDVPMA combined with near-infrared (NIR) laser irradiation elicited robust antitumor immunity, significantly suppressing primary tumor growth and metastasis, while establishing durable immune memory that prevented tumor recurrence. This study provides valuable insights into the development of nanomedicines for immunotherapy targeting tumors in a hypercoagulable state."

Journal • Breast Cancer • Cardiovascular • Hematological Disorders • Oncology • Solid Tumor • Thrombosis • STING

Fine-Tuning Photochemical Immunogenic Cell Death by a Panel of Verteporfin-Lipid Nanoparticles: A Data-Driven Approach. (PubMed, Small Sci) - "ICD marker exposure is proportional to the degree of phototoxicity and cellular uptake efficiency for all V-LNPs. These findings provide critical insights into the multiparametric mechanism underlying photochemical ICD induced by V-LNPs and can inform the rational design of photochemical LNP constructs for augmenting anticancer immune responses."

Journal • Oncology • Pancreatic Cancer • Solid Tumor

Hypoxic Tumor Microenvironment Promotes Hippo Pathway Transcriptional Activity to Enrich Glioma Stem Cells in the Peri-necrotic Niche of Glioblastoma (WFNOS 2025) - "AKT inhibition with Capivasertib reduced Zyx phosphorylation and Hippo transcription in hypoxia...Blocking TGFBR2 with inhibitor LY2109761 abolished TGF-β1-induced Hippo activation...In vivo, pharmacologic inhibition of YAP/TAZ with Verteporfin or genetic TAZ knockdown in the RCAS/tv-a mouse model reduced tumor burden and prolonged survival. Flow cytometry confirmed decreased CD133+/CD44+ GSCs in TAZ-deficient tumors. These results demonstrate hypoxia and TGF-β1 signaling to activate YAP/TAZ-driven Hippo signaling, promoting GSC maintenance in the peri-necrotic GBM niche."

Biomarker • Tumor microenvironment • Brain Cancer • Glioblastoma • Solid Tumor • CCN1 • CD133 • FOXM1 • OLIG2 • SOX2 • TAFAZZIN • TGFB1 • TGFBR2 • YAP1

NF2/Merlin loss induces upregulation of an alternative Wnt5a/b signaling pathway sensitive to YAP inhibition (WFNOS 2025) - "In primary NF2-mutant meningioma lines, targeting this pathway via blocking Wnt secretion with the inhibitor LGK974 or YAP signaling with verteporfin, which is FDA approved, results in decreased cell viability and proliferation in vitro. These results indicate activation of the Wnt5a/b-YAP/TAZ alternative signaling pathway in NF2-mutant meningeal and Schwann cells, and a potential therapeutic effect of blocking this pathway in NF2-mutant meningiomas with a previously-FDA approved inhibitor. Additional research is needed on the receptors and molecular mediators playing a role in this pathway and how these drugs may have therapeutic benefits in vivo"

Alzheimer's Disease • Ataxia • Brain Cancer • CNS Disorders • CNS Tumor • Cognitive Disorders • Meningioma • Movement Disorders • Oncology • Otorhinolaryngology • Solid Tumor • Ventriculomegaly • CTNNB1 • NF2

Synergistic Effects of HDAC Inhibition and Hippo Signaling Pathway Regulation in Glioblastoma (WFNOS 2025) - "In this study, we evaluated the therapeutic impact of combining the HDAC inhibitor SAHA (suberoylanilide hydroxamic acid) with Verteporfin, a Hippo signaling pathway regulator, in patient-derived GBM tumor spheres (TS13-64 and TS15-88). Our findings suggest that combined modulation of HDAC activity and Hippo pathway signaling represents a promising therapeutic strategy for GBM. This dual-targeted approach may overcome current treatment resistance and improve clinical outcomes in GBM patients."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor

Pulmonary-Targeted Nanoparticles Interrupt the Malignant Mechanical and Biochemical Signaling Crosstalk for Idiopathic Pulmonary Fibrosis Therapy. (PubMed, Adv Sci (Weinh)) - "Therefore, inhalable lung-targeted lipid nanoparticles (VB-RT NPs) are developed for co-delivering verteporfin and berbamine to effectively treat IPF by interrupting pulmonary mechanical-biochemical signaling malignant crosstalk...After being inhaled in a bleomycin model, VB-RT NPs inhibited fibroblast activation and promoted the transition of endothelial cell (EC)-like myofibroblasts to ECs, reducing endothelial-to-mesenchymal transition and fibrotic progression. Additionally, VB-RT NPs blocked the nuclear translocation of the mechanotransducers Yes-associated protein, interrupting fibrosis-related mechanotransduction pathways. The results demonstrate that VB-RT NPs effectively reversed dysregulated mechanical-biochemical signaling crosstalk in fibrotic lungs and halted fibrosis progression, offering a promising therapeutic approach for IPF."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Nanoengineered photosensitizers for photodynamic priming to overcome P-glycoprotein-mediated multidrug resistance. (PubMed, Photochem Photobiol) - "While photoactivation of verteporfin (VP), a photosensitizer, has demonstrated success for overcoming MDR through direct protein aggregation upon photoactivation and through adenosine triphosphate (ATP) depletion, the impact of VP's formulation on P-gp function and cellular energetics has not been fully characterized in this context...Photodynamic priming with NanoVP at sub-cytotoxic light doses enhanced P-gp substrate retention within the cells without damaging P-gp protein, indicating ATP depletion as the primary mode of functional inhibition. These findings highlighted NanoVP's clinical potential to enhance chemotherapeutic efficacy via photoactivation-based modulation of P-gp's function in multidrug-resistant cancers."

Journal • Oncology • ABCB1

MS4A1 regulates M1-polarized tumor-associated macrophage infiltration, angiogenesis, and cancer progression through the HIPPO pathway in lung adenocarcinoma. (PubMed, Cancer Immunol Immunother) - "In vivo experiments also demonstrated that verteporfin inhibited the in-situ tumor progression and ivonescimab enhanced the efficacy of immunotherapy in MS4A1 low tumor-bearing mouse. The MS4A1/M1 macrophage axis was identified as a crucial regulator of malignancy in LUAD, indicating MS4A1 as a promising novel therapeutic target for advanced LUAD treatment."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD20 • MS4A1

YAP activity protects against ventilator-induced lung injury. (PubMed, Front Physiol) - "Additional mice were treated with or without the YAP inhibitor verteporfin (VP) and with or without the YAP stimulator XMU-MP-1 (X) and then subjected to HVT...In contrast, after stimulation of YAP activity, the reduction in β-catenin was mitigated, the impairment of AEC regeneration was ameliorated, lung injury and fibrosis were alleviated. The results indicate stimulation of YAP activity alleviates VILI by promoting lung repair and inhibiting fibrosis development."

Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Bupivacaine exacerbates postoperative cognitive dysfunction by suppressing YES1-mediated YAP1 phosphorylation. (PubMed, Exp Brain Res) - "Treatment with verteporfin reversed the alleviating effects of YES1 overexpression on neuronal DNA damage and exacerbated POCD in mice. In conclusion, bupivacaine induces POCD by suppressing YES1 expression and YAP1 phosphorylation, leading to DNA damage."

Journal • Anesthesia • Cognitive Disorders • Oncology • YAP1 • YES1