Erivedge (vismodegib) / Curis, Roche - LARVOL DELTA

Successful Alternative Administration of Sonidegib in a Patient with Gorlin-Goltz Syndrome and Dysphagia: A Case Report. (PubMed, Case Rep Dermatol) - "Approved HH pathway inhibitors, like vismodegib and sonidegib, are supplied in capsule form. Patients who suffer from dysphagia may have problems swallowing these medications. This case report describes the successful use of an alternative administration of sonidegib in a patient with Gorlin-Goltz syndrome and dysphagia."

Journal • Basal Cell Carcinoma • Gastrointestinal Disorder • Non-melanoma Skin Cancer • Oncology • Otorhinolaryngology

Clinical Outcomes of Sonidegib in Vismodegib-Exposed Locally Advanced Basal Cell Carcinoma: Insights From a Multicenter Descriptive Study. (PubMed, J Skin Cancer) - "No novel AEs have been documented, and they were managed through dose adjustments or temporary interruptions. These findings suggest that sonidegib could still show efficacy and may still serve as a viable second-line option after prior Hh pathway suspension."

Clinical data • Journal • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

A Case Report of Promising Response to Combination Therapy With an Immune Checkpoint Inhibitor (Pembrolizumab) and Multi-Targeted Tyrosine Kinase Inhibitor (Pazopanib) in Metastatic De-Differentiated Chondrosarcoma. (PubMed, Cancer Rep (Hoboken)) - "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."

Checkpoint inhibition • IO biomarker • Journal • Atrial Fibrillation • Cardiovascular • Inherited Retinal Dystrophy • Musculoskeletal Diseases • Oncology • Ophthalmology • Pain • Sarcoma • Solid Tumor • IDH2 • PTCH1

Mohs Surgery Outcomes for Basal Cell Carcinoma Treated With Neoadjuvant Sonic Hedgehog Inhibitor. (PubMed, Int J Dermatol) - No abstract available

Journal • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

The Therapeutic Effect and Mechanism of Vismodegib on COPD: Focusing on NETs and Macrophage Polarization. (PubMed, Chem Biol Drug Des) - "Vismodegib may alleviate inflammation and tissue damage in COPD by inhibiting NETs-mediated M1 polarization of macrophages. This study is the first to propose the targeting of NET-driven macrophage polarization via Hedgehog inhibition as a novel therapeutic strategy for COPD, providing a new mechanistic framework for drug repurposing."

Journal • Chronic Obstructive Pulmonary Disease • Fibrosis • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • ELANE • IL17A • IL1B • IL6 • MPO • TNFA

Sonic Hedgehog Pathway Modulation in Medulloblastoma: Focus on Vismodegib (GDC-0449). (PubMed, Dev Neurobiol) - "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."

Journal • Review • Brain Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • PTCH1 • SMO

The 129S1/SvImJ Mouse Strain Is Resistant to the Effects of Early Embryonic Alcohol and Other Sonic Hedgehog Inhibitors. (PubMed, Birth Defects Res) - "129S1 embryos have higher expression of key Shh pathway genes and low apoptosis after alcohol, which may contribute to the alcohol-resistant phenotype seen in the 129S1/SvImJ strain, adding to the understanding of protective genetic factors in alcohol teratogenesis."

Journal • Preclinical • CNS Disorders • Genetic Disorders

Hedgehog-Wnt Crosstalk Orchestrates Submandibular Gland Morphogenesis in Mice. (PubMed, Genesis) - "Critically, the co-administration of the Wnt inhibitor XAV939 with vismodegib in ex vivo cultures partially rescued the branching defects caused by Hh inhibition. We conclude that Hh signaling promotes murine SMG morphogenesis, at least in part, by tonically inhibiting the Wnt pathway. This study unveils a novel inhibitory crosstalk between Hh and Wnt signaling that is essential for normal salivary gland development."

Journal • Preclinical • GLI1 • PTCH1

Regulatory Signaling Pathways in Ovarian Cancer Stem Cells: Their Role in Tumor Progression and Therapeutic Strategies. (PubMed, Iran Biomed J) - "Various therapeutic agents have been studied to target these pathways in OCSCs, including γ-secretase inhibitors (nirogacestat), smoothened inhibitors (vismodegib and sonidegib), and Wnt/β-catenin inhibitors (PRI-724 and ipafricept). To improve treatment outcomes, strategies involving combination approaches and personalized treatments need to be explored. This review aims to summarize current evidence on the role of Wnt/β-catenin, Notch, and Hedgehog signaling pathways in OCSCs and their therapeutic implications in ovarian cancer."

Journal • Oncology • Ovarian Cancer • Solid Tumor

Repurposing Itraconazole in Clinical Dermato-oncology Beyond Conventional Antifungal Use- A review. (PubMed, Clin Exp Dermatol) - "Unlike conventional SHH pathway inhibitors such as vismodegib and sonidegib, which exert their effect via direct binding to the transmembrane protein Smoothened (SMO), itraconazole impedes intracellular SMO trafficking, thereby attenuating downstream pathway activation. Despite encouraging preliminary evidence, further investigation through randomized controlled trials is warranted to optimize dosage regimens, define therapeutic windows, and explore synergistic potential with existing oncologic agents. The repositioning of itraconazole exemplifies the expanding interface between dermatology and oncology and highlights the promise of drug repurposing in cutaneous malignancies."

Journal • Basal Cell Carcinoma • Dermatology • Non-melanoma Skin Cancer • Oncology • Skin Cancer

N2M2/NOA-20: Phase I/IIa umbrella trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation. (ASCO 2024) - P1/2 | "Background: Patients with glioblastoma without MGMT promoter hypermethylation are unlikely to benefit from temozolomide (TMZ)...The alectinib and vismodegib subtrials were closed since no molecularly matching patients were accrued; the idasanutlin subtrial was closed prior to the optimal dose at nine patients at discretion of the company providing the drug... N 2 M 2 allows for elaborate molecular testing being integrated into the treatment decision and efficient determination of treatment activity for patients with newly diagnosed glioblastoma. There is clinical activity of temsirolimus in patients with tumors harboring an activated mTOR pathway although this is not positively prognostic without mTOR inhibition; there is no clinical activity for asunercept and atezolizumab in not molecularly selected patients and also palbociclib in molecularly selected patients."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDK4 • CDKN2A • CDKN2B

Proteome microarray-guided identification of mycobacterial antigens and ELISA-based peptide mapping for improved serological detection of Mycobacterium bovis infection in European badgers. (PubMed, J Clin Microbiol) - "This strategy identified Rv3616c as a novel antigen with promising diagnostic test potential for M. bovis infection in badgers...These synthetic peptides are scalable, cost-effective, and adaptable to different diagnostic platforms. The findings reveal an antigen with diagnostic potential that could inform the development of new tests for bTB surveillance in wildlife, supporting One Health principles and global tuberculosis elimination strategies."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Alcian blue-positive stromal phenotype in basal cell carcinoma is associated with progression on first-line hedgehog inhibitors. (PubMed, J Pathol Clin Res) - "Hedgehog pathway inhibitors (HHIs; vismodegib/sonidegib) constitute standard first-line treatment, yet individual responses vary and no histopathological biomarker predicting therapeutic outcome exists. Our findings identify diffuse AB-positive stroma as a readily detectable feature of histologically aggressive BCC and as a candidate biomarker associated with progression under HHI treatment. Because AB staining is routine, inexpensive, and easily standardized, this phenotype represents an immediately implementable readout for prospective validation and a potential link between extracellular-matrix remodeling and therapy resistance in BCC."

Biomarker • Journal • Retrospective data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Nodular Basal Cell Carcinoma

Temporal regulation of the Ihh-PTHrP signaling axis modulates condylar development via angiogenesis. (PubMed, Differentiation) - "Furthermore, at E15.5, expression of key components of the Ihh-PTHrP signaling axis (Gli1, Ptch1, and PTHrP) was significantly downregulated in the experimental group relative to controls. These findings suggest that vismodegib disrupts TMJ development by inhibiting the Ihh-PTHrP signaling pathway, thereby altering angiogenesis in the condyle and ultimately impairing cartilage growth and structural integrity."

Journal • CD31 • CD34 • GLI1 • PECAM1 • PTCH1

A071401: Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas (clinicaltrials.gov) - P2 | N=124 | Recruiting | Sponsor: Alliance for Clinical Trials in Oncology | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial primary completion date • Brain Cancer • Meningioma • Oncology • Solid Tumor • AKT1 • CCND1 • CCND2 • CCND3 • CCNE1 • CDK4 • CDK6 • CDKN2A • NF2 • PIK3CA • PTCH1 • PTEN • SMO

Resistance to SMO Inhibitors in Advanced Basal Cell Carcinoma: A Case Highlighting the Role of Molecular Tumor Profiling. (PubMed, Int J Mol Sci) - "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."

Journal • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • FGFR1 • NOTCH1 • PTCH1 • SMO • TP53

Targeting SPP1-CD44-Hedgehog Axis Elicits Therapeutic Effects in Hepatocellular Carcinoma by Suppressing Intratumoral Fibrosis. (PubMed, Cancer Sci) - "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."

Journal • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Oncology • Solid Tumor • SPP1

Vismodegib and Sonidegib Are Associated With an Elevated Reporting Odds of Squamous Cell Carcinoma; a Comparative Pharmacovigilance Study of the FDA Adverse Events Reporting System (FAERS). (PubMed, Australas J Dermatol) - "Vismodegib has a significantly higher ROR for alopecia and taste symptoms, while sonidegib was associated with neutropenia, which is a novel finding. Both HIs are associated with an increased ROR for cSCC, which persists despite stringent controls and does not parallel total cSCC cases reported to FAERS. These data suggest that HIs increase the risk of cSCC above the baseline expected in this patient population."

Adverse events • Journal • Alopecia • Basal Cell Carcinoma • Hematological Disorders • Immunology • Musculoskeletal Pain • Neutropenia • Non-melanoma Skin Cancer • Oncology • Pain • Squamous Cell Carcinoma

Vismodegib and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Suspended | Sponsor: Dwight Owen | Recruiting ➔ Suspended

Trial suspension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Activated T cells degrade extracellular proteins to enhance effector functions. (PubMed, Cell Rep) - "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."

Journal • Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CD8 • PD-1 • TFE3

Dual Hedgehog/GLI1 and PI3K/Akt/mTOR Targeting Possesses Higher Efficacy to Inhibit T-Cell Acute Lymphoblastic Leukemia Growth. (PubMed, Cells) - "Cells were treated with the Gli1 inhibitor Gant-61, the Smoothened inhibitors GDC-0449 and Glasdegib, the Akt inhibitor MK-2206, and the mTOR inhibitor RAD001, both alone and in combination. These findings demonstrate a functional interaction between Hh/Gli1 and PI3K/Akt pathways in T-ALL and identify Gli1 as a critical, druggable node. Dual targeting of Gli1 and Akt represents a potential therapeutic strategy to overcome resistance and improve treatment outcomes in T-ALL."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • GLI1

Real-World Treatment Patterns of Patients with Basal Cell Carcinoma Using Sonidegib and Vismodegib: Discontinuation Rates and Clinical Conditions During Treatment. (PubMed, Dermatol Ther (Heidelb)) - "In the real-world setting, sonidegib-treated patients remained on treatment longer than vismodegib-treated patients and were less likely to experience pharmacologically relevant clinical conditions."

HEOR • Journal • Real-world evidence • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Chondrosarcoma organoids reveal SHH pathway activation driven by PTCH1 and BCOR alterations. (PubMed, Sci Rep) - "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."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Transplantation • BCOR • PTCH1

P023 Metastatic basal cell carcinoma with bone marrow involvement: a rare case report. (PubMed, Br J Dermatol) - "The patient's presentation with pancytopenia underscores the importance of considering metastatic BCC in cases of unexplained haematological abnormalities in patients with a history of aggressive BCC. Systemic therapies such as vismodegib offer a targeted treatment option and represent a significant advancement in managing metastatic BCC."

Journal • Basal Cell Carcinoma • Hematological Disorders • Hematological Malignancies • Non-melanoma Skin Cancer • Oncology

Cutaneous squamous cell carcinoma while on vismodegib therapy for locally advanced basal cell carcinoma. (PubMed, Actas Dermosifiliogr) - No abstract available

Journal • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer