Trial reportEuropean journal of cancer (Oxford, England : 1990)2012
A phase II study of RO4929097 in metastatic colorectal cancer.
Trial report in European journal of cancer (Oxford, England : 1990), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 147 citations in OpenAlex.
- Phase 2 study of RO4929097, a gamma-secretase inhibitor, in metastatic melanoma: SWOG 0933.Cancer · 2015Trial
- A phase II study of the gamma secretase inhibitor RO4929097 in patients with previously treated metastatic pancreatic adenocarcinoma.Investigational new drugs · 2014Trial
- Decoding notch signaling pathway: an updated insight into its role in colorectal cancer progression and therapy.Cancer cell international · 2026Review
- Tumour Jagged1 expression as a prognostic marker of bevacizumab response and modulation of 5-fluorouracil efficacy through γ-secretase inhibition in colorectal cancer.Gastroenterology report · 2026Article
- Emerging roles of Notch signaling in the tumor microenvironment of digestive system cancers.Frontiers in molecular biosciences · 2026Review
- YTHDF1 targets the chemotherapy response by suppressing NOTCH1-induced stemness in colorectal cancer.Signal transduction and targeted therapy · 2025Article
- Review
- Structural basis of human γ-secretase inhibition by anticancer clinical compounds.Nature structural & molecular biology · 2025Article
- Natural flavonoid Orientin restricts 5-Fluorouracil induced cancer stem cells mediated angiogenesis by regulating HIF1α and VEGFA in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Targeted Cancer Stem Cell Therapeutics: An Update.Current topics in medicinal chemistry · 2025Review
- Targeted Treatment against Cancer Stem Cells in Colorectal Cancer.International journal of molecular sciences · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Non-canonical non-genomic morphogen signaling in anucleate platelets: a critical determinant of prothrombotic function in circulation.Cell communication and signaling : CCS · 2024Review
- Colorectal Cancer Stem Cells and Targeted Agents.Pharmaceutics · 2023Review
- Article
- The Intricate Notch Signaling Dynamics in Therapeutic Realms of Cancer.ACS pharmacology & translational science · 2023Review
- Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World journal of gastroenterology · 2023Review
- Notch receptor/ligand diversity: contribution to colorectal cancer stem cell heterogeneity.Frontiers in cell and developmental biology · 2023Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe Notch signalling pathway is activated in a variety of malignancies and has been implicated in colorectal cancer progression. One of the first steps in the Notch pathway activation is mediated by γ-secretase, a proteolytic enzyme which produces an activated intracellular Notch (ICN). RO4929097 is a selective inhibitor of γ-secretase. We tested the activity of RO4929097 in patients with metastatic, refractory colorectal cancer. PATIENTS AND
methodsPatients with metastatic colorectal cancer who had received at least two prior lines of systemic chemotherapy were enrolled on the study. Patients were treated with RO4929097 at its recommended phase II dose of 20mg daily, 3 days on and 4 days off continuously. Cycle length was 28 days. Imaging was performed every two cycles. Archival tissue specimens were stained immunohistochemically for components of the notch pathway: Notch1, ICN and the downstream target HES1.
resultsThirty-seven patients were enrolled of whom 33 were evaluable for toxicity and response. Immunohistochemical analysis of archival tissues demonstrated positive staining for the notch receptor as well as intracellular notch and the downstream gene HES1 in the majority of patients. Nevertheless, no objective radiographic responses were observed in this group and only six patients had stable disease as their best response. Median PFS was 1.8 months and median overall survival (OS) was 6.0 months.
conclusionIn this study of RO4929097 in patients with refractory metastatic colorectal cancer, no radiographic responses were seen and time to progression was short, which suggests that RO4929097 at the study dose and schedule has minimal single agent activity in this malignancy.
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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.