Prospects encompass the enhancement of drug delivery methods, the integration of SHH inhibitors with alternative therapeutics, and the advancement of next-generation inhibitors to surmount resistance. Hence, these developments offer potential for improving outcomes in SHH-MB while reducing side effects, especially in pediatric populations.

This case report is a valuable example of promising emerging systemic therapies for advanced DDCS, where the present standard of care lacks a repertoire of effective therapies.

Profiling inflammatory mediators revealed significant modulation upon treatment with SMO inhibitors, possibly affecting chemotactic and immune functions. Collectively, these findings provide deeper insight into the role of the Hh pathway in melanoma and support the potential repurposing of Hh inhibitors as therapeutic agents for melanoma.

Accordingly, current targeted therapies for locally advanced, unresectable, or metastatic BCC focus on SMO inhibition, using orally administered drugs such as vismodegib and sonidegib. To our knowledge, this is the first report documenting a sonidegib resistance mechanism in BCC that is independent of HH pathway mutations. This case highlights the complexity of resistance mechanisms to HH inhibitors and underscores the critical need for comprehensive molecular tumor profiling prior to initiating targeted therapy.

The linker-payload system was stable in plasma yet released gradually cyclopamine at pH 5.5. These results suggest the feasibility of using natural products as payloads for the construction of ADCs to inhibit HH signalling in cancer cells.

Pharmacological inhibition of GLI1 with the SMO inhibitor vismodegib suppressed HSC activation in vitro and reduced fibrosis and tumor growth in vivo. These findings indicate that SPP1 promotes intratumoral fibrosis and HCC progression through the SPP1-CD44-GLI1 axis, highlighting its potential as a prognostic biomarker and therapeutic target. Inhibition of SPP1-CD44-Hedgehog signaling may provide a promising strategy to mitigate fibrosis and improve HCC patient outcomes.

This functional defect is rescued by treatment with Vismodegib, a TFE3-inducing drug. Our findings reveal lysosome-mediated extracellular protein catabolism as an important metabolic pathway supporting T cell immunity.

Organoid-based drug sensitivity testing was conducted using vismodegib, a Sonic Hedgehog (SHH) pathway inhibitor...We established the first PDO models of chondrosarcoma that faithfully recapitulate key tumor features. These models provide a valuable preclinical platform for dissecting molecular pathogenesis and for advancing the development of targeted therapeutic strategies in this intractable malignancy.

P2, N=16, Completed, Melanoma Institute Australia | Recruiting --> Completed | Trial completion date: Jun 2026 --> Mar 2025 | Trial primary completion date: Jun 2026 --> Mar 2025

P2, N=20, Recruiting, Melanoma Institute Australia | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P2, N=660, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Jan 2028 --> Oct 2031 | Trial primary completion date: Nov 2025 --> Oct 2028

Taken together, these findings establish a mechanistic foundation for a proposed therapeutic optimization strategy: Reducing vismodegib dosing while leveraging its inhibition-driven elevation of simvastatin systemic/tissue exposure, thereby mitigating dose-limiting skeletal toxicity while maintaining anti-tumor efficacy. This mechanism-based strategy provides a clinically actionable framework for pediatric medulloblastoma with urgent unmet therapeutic needs.