SMO (Smoothened Frizzled Class Receptor)

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.

Despite significant advances, genotype-phenotype correlations, mutation frequencies and coexistence, clonality, and other associations remain incompletely understood. Larger tumor cohorts and robust meta-analyses are required to clarify these associations and to leverage the development of personalized therapeutic strategies.

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.

Altogether, convergent evidence suggests that activating upstream HH signaling is necessary but not sufficient for BCC formation. This evolving view of BCC has important implications for our basic understanding of these tumors, for our interpretation of findings from BCC mouse models, and for guiding treatment.

In vivo, xenotransplantation experiments demonstrated that Smo silencing led to slower tumor growth with reduced tumor volume and weight. Overall, Smo gene silencing holds great potential as a novel molecular-targeted therapy approach for NKTCL by effectively suppressing cell proliferation and promoting apoptosis.

Solasodine inhibited the proliferation of AGS and MKN74 gastric cancer cells and regulated cell cycle (Cyclin D1 and p27) and apoptosis (Bax and Bcl-2) markers in a dose-dependent manner, consistent with the Gli1/2 inhibitor Gant61 but not the Smo inhibitor vismodegib...Moreover, solasodine inhibited Gli1 rather than Smo expression in Hh signaling overexpressed Ptch (-/-) MEF cells. Our findings demonstrate that solasodine inhibits gastric cancer proliferation by targeting Hh/Gli1 signaling, underscoring its potential as a potent agent for prevention and/or inhibition of gastric cancer.

Vismodegib was well tolerated with mainly grade 1-2 toxicities, but it did not meet the primary end point. Select patients with specific SMO and PTCH1 alterations had notable responses, warranting further comprehensive molecular analyses to elucidate resistance mechanisms.

This comprehensive transcriptomic characterization of T-cell exclusion in PM reveals that targeting cilium-based Hedgehog signaling, in addition to multiple other actionable drug targets, could enhance the efficacy of ICB treatment in PM.

This study provides regional insight into the molecular landscape of meningiomas in our population. While routine molecular profiling adds value to classification and prognostication, broader implementation may be limited by cost and panel coverage constraints.

This study revealed that 70% of OGMs harbor SMO, AKT1, and PIK3CA mutations, influencing tumor behavior, symptoms, and outcomes, supporting molecular profiling for personalized treatment in OGM management.

These results suggest that NCOA4 is downregulated in gliomas and that its overexpression predicts better overall survival in glioma patients. Mechanistically, NCOA4 overexpression inhibits the progression of glioma by suppressing the SHH pathway.