Trial reportCancer chemotherapy and pharmacology2016
Pharmacodynamic study of the oral hedgehog pathway inhibitor, vismodegib, in patients with metastatic castration-resistant prostate cancer.
Trial report in Cancer chemotherapy and pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02115828 (A Pharmacodynamic Study of Vismodegib in Men With Metastatic Castration-resistant Prostate Cancer), which is not on this map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Pharmacodynamic Study of Vismodegib in Men With Metastatic Castration-resistant Prostate Cancer (mCRPC) With Accessible Metastatic Lesions for Tumor Biopsy
Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- 20 years of taxane therapy in prostate cancer - the past, present and future.Nature reviews. Urology · 2026Review
- Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy.Annals of medicine · 2025Review
- Stromal androgen signaling governs essential niches in supporting prostate development and tumorigenesis.Oncogene · 2024Review
- Deciphering the Tumor Microenvironment in Prostate Cancer: A Focus on the Stromal Component.Cancers · 2024Review
- MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression.JCI insight · 2023Article
- Prostate Cancer Stem Cells: Biology and Treatment Implications.International journal of molecular sciences · 2023Review
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Signaling Pathways and Targeted Therapies for Stem Cells in Prostate Cancer.ACS pharmacology & translational science · 2022Review
- The use of hedgehog antagonists in cancer therapy: a comparison of clinical outcomes and gene expression analyses.Cancer biology & therapy · 2020Article
- Bone microenvironment signaling of cancer stem cells as a therapeutic target in metastatic prostate cancer.Cell biology and toxicology · 2020Review
- Smoothened-dependent and -independent pathways in mammalian noncanonical Hedgehog signaling.The Journal of biological chemistry · 2019Article
- Review
- Review
- Reproducibility of academic preclinical translational research: lessons from the development of Hedgehog pathway inhibitors to treat cancer.Open biology · 2018Review
- Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer.The American journal of pathology · 2018Article
- Hedgehog in prostate cancer explained.Oncoscience · 2018Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
purposeHedgehog (Hh) pathway signaling has been implicated in prostate cancer tumorigenesis and metastatic development and may be upregulated even further in the castration-resistant state. We hypothesized that antagonism of the Hh pathway with vismodegib in men with metastatic castration-resistant prostate cancer (mCRPC) would result in pathway engagement, inhibition and perhaps induce measurable clinical responses in patients.
methodsThis is a single-arm study of oral daily vismodegib in men with mCRPC. All patients were required to have biopsies of the tumor and skin (a surrogate tissue) at baseline and after 4 weeks of therapy. Ten patients were planned for enrollment. The primary outcome was the pharmacodynamic assessment of Gli1 mRNA suppression with vismodegib in tumor tissue. Secondary outcomes included PSA response rates, progression-free survival (PFS), overall survival (OS) and safety.
resultsNine patients were enrolled. Gli1 mRNA was significantly suppressed by vismodegib in both tumor tissue (4/7 evaluable biopsies, 57%) and benign skin biopsies (6/8 evaluable biopsies, 75%). The median number of treatment cycles completed was three, with a median PFS of 1.9 months (95% CI 1.3, NA), and a median OS of 7.04 months (95% CI 3.4, NA). No patient achieved a PSA reduction or a measurable tumor response. Safety data were consistent with the known toxicities of vismodegib.
conclusionsHh signaling, as measured by Gli1 mRNA expression in mCRPC tissues, was suppressed with vismodegib in the majority of patients. Despite this pharmacodynamic response that indicated target inhibition in some patients, there was no apparent signal of clinical activity. Vismodegib will not be developed further as monotherapy in mCRPC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.