Erivedge (vismodegib) / Curis, Roche - LARVOL DELTA

A Review of Hedgehog Pathway Inhibitors in Combination Therapy for Basal Cell Carcinoma (AAD 2026) - "A total of nine studies were included, involving either vismodegib or sonidegib combined with concomitant therapy of either itraconazole, radiation therapy, photodynamic therapy (PDT), pembrolizumab, intratumoral immunotherapy ASN-002, or surgical debulking. Lastly, 75% of combination therapy studies reported a more tolerable AE when compared to monotherapy. Combination strategies represent a promising avenue to optimize efficacy, improve tolerability, and expand therapeutic options for patients with BCC."

Combination therapy • Review • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Non-Surgical Management Options for Basal Cell and Squamous Cell Carcinomas: A Comparative Literature Review (AAD 2026) - "Topical agents (5-fluorouracil, imiquimod) were effective for superficial BCC and SCC in situ, with imiquimod achieving higher long-term tumor-free survival and 5-FU favored for field therapy...Hedgehog inhibitors (vismodegib, sonidegib) yielded responses in advanced BCC, though discontinuation was common due to class toxicities...In advanced disease, hedgehog inhibitors for BCC and cemiplimab for cSCC provide durable responses. A risk-stratified approach integrating tumor biology, site, patient values, and resources can guide individualized nonsurgical management."

Review • Basal Cell Carcinoma • Bowens Disease • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Comparison of Smoothened Inhibitors in Treating Advanced Basal Cell Carcinoma: Multidisciplinary Expert Opinions and Clinical Experiences (AAD 2026) - "Landmark studies ERIVANCE and BOLT facilitated FDA approval of vismodegib in 2012 and sonidegib in 2015, respectively, and provided valuable insights into SMOi efficacy, dosing, pharmacokinetics, and adverse effects (AE). These findings highlight the lack of uniformity, as well as familiarity, with the therapeutic options of SMOi for advanced BCC. Updating SMOi clinical guidelines and the creation of management strategies, including considerations for AE, dosing options, and drug switching, are needed to improve and standardize patient care."

Clinical • Metastases • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer

Metastatic Basal Cell Carcinoma Presenting as Large Bowel Obstruction: A Rare Manifestation with Novel Molecular Insights (AAD 2026) - "He received vismodegib, surgery, and radiotherapy, followed by 32 months of stable disease...He was started on pembrolizumab for high PD-L1 expression; however, disease progressed, and he was ultimately transitioned to hospice...Collectively, these molecular findings may contribute to aggressive tumor biology and suggest therapeutic vulnerabilities beyond Hedgehog inhibition. This underscores the importance of early recognition and treatment of high-risk BCC and the evolving role of molecular profiling in refining prognosis and guiding therapeutic strategies."

IO biomarker • Metastases • Tumor mutational burden • Basal Cell Carcinoma • Gastroenterology • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • ARID1A • FGFR2 • PD-L1 • PTCH1 • SMO • TMB • TP53

Impact of Reporter Type on Signal Detection of Cancer Therapy-Induced Alopecia: A Hypothesis-Generating Study Using the FDA Adverse Event Reporting System. (PubMed, Pharmaceuticals (Basel)) - "In the analysis restricted to HCP reports, the highest ROR was observed for vismodegib [23.92 (21.86-26.17)], whereas that for docetaxel markedly decreased to 3.68 (3.48-3.89). Reporter characteristics substantially influence the detection of alopecia signals, with patients amplifying signals reflecting psychological harm and HCPs amplifying signals reflecting pharmacological plausibility. These findings should be interpreted as hypothesis-generating and warrant further validation using prospective or clinical datasets."

Adverse events • Journal • Alopecia • Breast Cancer • Immunology • Oncology • Solid Tumor

Dual targeting GLI1 and EZH2 for treatment of invasive breast cancer (AACR 2026) - "The CompuSyn for drug synergy analysis, both the Combination Index (CI) and Dose Reduction Index (DRI) indicated that the combination therapy exhibited significant synergistic effects, where Vismodegib could reduce the dose by ~52-fold, while GSK126 could reduce the dose by ~22-fold. Form the findings, we believe that dual targeting GLI1-EZH2 has potential to become a novel and effective combination treatment for invasive breast cancer in the clinical setting."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCND1 • EZH2 • GLI1 • MYC

Hair loss in cancer patients receiving small molecule inhibitors: Evidence from clinical trials (AACR 2026) - "Hedgehog pathway inhibitors induced the highest overall rates, ranging from 20-30% with saridegib and glasdegib, and up to 63% with vismodegib. FGFR inhibitors (pemigatinib, infigratinib) and other kinase inhibitors (ripretinib, vemurafenib, sorafenib, AZD0424) demonstrated moderate rates (22-48%). Lower alopecia incidence was reported with aromatase inhibitors (anastrozole, lenostrozole) and the aurora B kinase inhibitor BI 811283, ranging from 9 to 21%...The higher incidences seen with Hedgehog inhibitors, compared with aromatase inhibitors, highlight how pathway-specific disruption of follicular signaling contributes to hair loss. Further research into the molecular mechanisms of these agents may help clinicians better anticipate and manage this side effect."

Clinical • Oncology • BRAF

Integrative pathway analysis of I-SPY2 HER2+ breast cancers reveals drug-repurposing opportunities (AACR 2026) - "Growth-factor/RTK bypass (PI3K/AKT) and DNA repair & oxidative stress defense were strongly upregulated in non-responders within BP-HER2, revealing actionable nodes involving PI3K/AKT (alpelisib, capivasertib), IGF1R (linsitinib), MET (crizotinib, capmatinib), and DNA repair (PARP inhibitors). Notably, metabolic rewiring and lipid homeostasis—targetable by vismodegib and sonidegib—were upregulated in non-responders across both BP subtypes, reflecting a shared metabolic vulnerability. Luminal biology-linked transcriptional programs may persist within the HER2+ BP-HER2 subtype and contribute to resistance... Luminal biology-linked transcriptional programs may persist within the HER2+ BP-HER2 subtype and contribute to resistance. BP-HER2 non-responders exhibit coordinated activation of RTK-bypass and DNA repair pathways, exposing therapeutic vulnerabilities targetable by existing agents. Furthermore, targeting lipid metabolic reprogramming alongside anti-HER2 therapy..."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Clinicopathologic and Molecular Characterization of Trichoblastic Carcinoma (USCAP 2026) - "Management included Mohs surgery (1/6, 17%), surgical excision (2/6, 33%) and vismodegib (1/6, 17%)... Recurrent PTCH1 alterations occur in TC, often in cases with higher-grade morphology and infiltrative borders. We suspect the TC from the scalp with a HRAS mutation may have arisen in association with an unsampled nevus sebaceus, which are characterized by HRAS alterations. Overall, the presence of recurrent PTCH1 gene mutations suggests that sporadic TC are genetically related to BCC, but that lower-grade lesions may have alternative drivers."

Clinical • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • CDKN2A • HRAS • PTCH1 • TP53

Locally Advanced Basal Cell Carcinoma With Orbital Invasion: Treatment With Neoadjuvant Hedgehog Pathway Inhibition and Palliative Enucleation. (PubMed, Cureus) - "The patient underwent left eye enucleation and reported complete resolution of pain. He showed no evidence of residual disease four months after completion of vismodegib therapy. This report highlights a rare case of locally advanced periocular BCC with orbital invasion managed with neoadjuvant hedgehog pathway inhibition and palliative enucleation."

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

GDC-0449 and Erlotinib Hydrochloride With or Without Gemcitabine Hydrochloride in Treating Patients With Metastatic Pancreatic Cancer or Solid Tumors That Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=55 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • BCL2

L-Carnitine in Dermatology: A Systematic Review of Therapeutic Potential and Biomarker Applications. (PubMed, J Cutan Med Surg) - "Systemic L-carnitine mitigates inflammation, oxidative stress, and treatment-related side effects (eg, from corticosteroids, isotretinoin, vismodegib) while improving skin elasticity, microcirculation, wound healing, and fibrosis in conditions like Raynaud's disease, venous leg ulcers, and sclerotic disorders. Its biomarker potential enhances disease insights and personalized care. Further dermatology-specific trials are needed to optimize dosing, formulations, and long-term safety, particularly regarding trimethylamine-N-oxide-related cardiovascular risks."

Biomarker • Journal • Review • Acne Vulgaris • Cardiovascular • Dermatology • Fibrosis • Immunology • Melanoma • Metabolic Disorders • Novel Coronavirus Disease • Oncology • Rheumatology • Solid Tumor • Venous Ulcer

Topical delivery of Vismodegib using fourth-generation PAMAM dendrimers: a potential treatment for Kaposi's sarcoma. (PubMed, Int J Pharm) - "Notably, G4-OH@VDG exhibited the most favorable therapeutic profile, including significant reduction of cell viability and inhibition of cell migration at sublethal concentrations. Overall, these results demonstrate that the combination of drug repurposing and dendrimer-based nanotechnology for topical delivery enhances the therapeutic performance of VDG in in vitro models of Kaposi's sarcoma."

Journal • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor

Analysis of rare clinical scenario in advanced/metastatic basal cell carcinoma (BCC) patients of cemiplimab therapy after progression on vismodegib (Sarcoma-RC 2026) - P2 | "Legal entity responsible for the study The authors. Funding Has not received any funding."

Clinical • Metastases • Basal Cell Carcinoma • Cardiovascular • Gastroenterology • Hepatology • Melanoma • Myocardial Infarction • Non-melanoma Skin Cancer • Oncology • Osteosarcoma • Sarcoma • Skin Cancer • Solid Tumor

Sonic Hedgehog-Gli1 signaling promotes microglial activation via the IKKβ/NF-κB pathway. (PubMed, Acta Pharmacol Sin) - "Notably, treatment with the small-molecule SMO inhibitor GDC-0449 (vismodegib) alleviated neuroinflammation and protected dopaminergic neurons in mice subjected to intracranial LPS challenge. Conversely, microglia-specific Ptch1 knockout exacerbated susceptibility to LPS-induced neuroinflammation and dopaminergic neuronal loss. Collectively, these findings demonstrate that microglial Shh-Gli1 signaling promotes microglial inflammatory activation, establishing the pivotal role of this pathway in microglia-driven neuroinflammation and subsequent dopaminergic neuronal injuries."

Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • GLI1 • PTCH1 • SHH

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR) (clinicaltrials.gov) - P2 | N=720 | Recruiting | Sponsor: Canadian Cancer Trials Group | Trial primary completion date: Jan 2026 ➔ Dec 2026

Pan tumor • Trial primary completion date • Tumor mutational burden • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BRAF

Blocking SHH Pathway Reduces the in Vitro Malignant Behavior of Uterine Leiomyosarcoma via Pharmacological or Genetic Inhibition of SMO (ISGE 2026) - "Pharmacological inhibition employed two SMO antagonists (GDC-0449 and LDE225) at IC50-determined concentrations (GDC-0449: 40 µM; LDE225: 300 µM). SMO is overexpressed in uterine LMS and its pharmacologic or genetic inhibition attenuates Hedgehog pathway readouts and reduces malignant cell behaviors in vitro. These results support further evaluation of SMO-targeted strategies for uterine smooth muscle neoplasms."

IO biomarker • Preclinical • Leiomyosarcoma • Sarcoma • Solid Tumor • Uterine Leiomyosarcoma • BCL2 • BMP4 • CCND1 • GLI1 • GLI2 • PTCH1 • SMO

Fractional ablative laser-enhanced transdermal delivery of vismodegib: systematic evaluation of microporation parameters and permeation kinetics. (PubMed, Int J Pharm) - "Drug quantities within skin layers, cumulative delivery, delivery efficiency, and topical selectivity were additionally studied and reported. Fractional ablative laser treatment substantially enhanced transdermal permeation of vismodegib into and through dermal tissues."

Journal • Aesthetic Medicine

Actin-related protein 6 regulates the Hedgehog signaling pathway: Molecular basis for stemness maintenance of hepatoma cells. (PubMed, Cytojournal) - "Vismodegib reversed the promoting effect of ACTR6 on the Hh signaling pathway and stem-related proteins in cells. ACTR6 regulates the molecular basis of stemness maintenance of liver cancer cells through the Hh signaling pathway and promotes the occurrence of liver cancer. This study provides possible targets for the clinical treatment of liver cancer."

Journal • Brain Cancer • Glioma • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • NANOG • PTCH1 • SHH • TCF4 • YBX1

Severe Necrotizing Locally Advanced Basal Cell Carcinoma With Osteomyelitis. (PubMed, Adv Skin Wound Care) - "In this case report, a 57-year-old female without significant past medical history presented with a 5-year history of a chronic progressive ulcer involving the neck and back. Histopathological study of the tissue identified nodular and infiltrative BCC, prompting further multidisciplinary treatment and management with vismodegib, radiation, and surgery."

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

Vismodegib and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Dwight Owen | Suspended ➔ Recruiting | Trial completion date: Dec 2026 ➔ Dec 2027

Enrollment open • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD4 • EGFR • PD-L1

Novel green-emissive carbon dots as a dual-purpose fluorometric tool for sensitive vismodegib detection and pharmacokinetic analysis. (PubMed, Anal Methods) - "Validation in human serum and urine samples confirmed the method's applicability for real-sample analysis, showing excellent agreement with UPLC results. The proposed G-N@CDs system was further employed for pharmacokinetic profiling of VISMO following oral administration, providing accurate concentration-time data that underscore its potential as a robust and cost-effective alternative to conventional chromatographic assays."

Journal • PK/PD data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

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