PTCH1 (Patched 1)

Increased levels of Gli3 repressor (Gli3-REP) and decreased GSK-3β phosphorylation further confirmed Hedgehog pathway inhibition. In conclusion, the current study provides the first evidence that CAN, CGA, and their combination modulate the Hedgehog pathway, suggesting their potential as novel therapeutic strategies for IPF.

The breakpoint was identical to those in the previously reported cases. Taken together, these findings suggest that PTCH1::GLI2 fusion may define a distinctive subtype of gastric mesenchymal tumors within the GLI1/GLI2-altered spectrum.

We concluded for the first time that the combination of SOR and ASH-AE generates antagonistic antitumor effect in HepG2 cells. Moreover, ASH-AE can inhibit proliferation of HepG2 cells and mitigate sorafenib-induced resistance-associated markers in HepG2 cells by targeting CD90+ cells via Hedgehog pathway modulation.

Around 5-6% of MBs are associated with inherited cancer predisposition syndromes, with common genetic variants including PTCH1, SUFU, TP53, and SMO. This report describes the first pediatric patient harboring a CHEK2 germline variant of uncertain significance and developing a EA- MB localized at the trigeminal nerve and subsequent CNS and EN metastases.

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.

Chemoprevention (e.g., nicotinamide) and targeted therapies (hedgehog inhibitors; Programmed Death-1 blockade) represent key translational levers for care innovation. (5) Integrating structured dermatologic surveillance with molecularly informed prevention and therapy should be standard in survivorship pathways for hematopoietic stem cell transplantation/Radiotherapy-exposed patients.

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.

P2, N=124, Recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Jan 2026 --> Jan 2027

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.

This method is particularly suited for studying how oncogenic signaling pathways such as Hh shape the immune landscape during tumor initiation, progression, or therapeutic response. Overall, the protocol offers a versatile platform for coupling gene expression mapping with immune contexture analysis in preclinical models of skin cancer.

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.