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.

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).

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.

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, progesterone receptor; qRT-PCR, quantitative real-time polymerase chain reaction; RT, room temperature; Sili, silibinin; si-RNAs, small interfering RNAs; TNBC, triple-negative breast cancer; VP, verteporfin; YAP, Yes-associated protein.

P2, N=90, Recruiting, Theralase® Technologies Inc. | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Jun 2026 --> Dec 2026

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.

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.

P1/2, N=48, Recruiting, Kiora Pharmaceuticals, Inc. | N=12 --> 48

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.

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.

This case suggests the potential for aggressive mycosis fungoides behavior despite indolent histopathological characteristics. Initial nail involvement might serve as a clinical marker of atypical progression. The limitations of Ki-67 alone suggest the need for comprehensive prognostic models that incorporate molecular biomarkers, such as thymocyte selection-associated high mobility group box, CD30, and T-cell receptor clonality.

P1, N=130, Suspended, Fox Chase Cancer Center | Recruiting --> Suspended