ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Notch Pathway Inhibition Using PF-03084014, a γ-Secretase Inhibitor (GSI), Enhances the Antitumor Effect of Docetaxel in Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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
59 citing papers in PubMed, 95 citations in OpenAlex.
- 20 years of taxane therapy in prostate cancer - the past, present and future.Nature reviews. Urology · 2026Review
- Tumor-associated macrophages promote chemoresistance to Paclitaxel via activating NOTCH2-JAG1 juxtacrine signaling.Molecular cancer · 2026Article
- Loss of IL1RA promotes prostate cancer growth and metastasis by activating Akt signaling pathway.PloS one · 2026Article
- Unravelling therapeutic resistance: role of cancer stem cell and microRNA in metastatic prostate cancer.Frontiers in molecular biosciences · 2026Review
- The Notch signaling pathway in regulating bone and cartilage homeostasis: novel insights into the pathogenesis and therapeutics of osteoarthritis.Cell communication and signaling : CCS · 2025Review
- Signalling pathways in a nutshell: from pathogenesis to therapeutical implications in prostate cancer.Annals of medicine · 2025Review
- Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy.Annals of medicine · 2025Review
- Docetaxel Administration via Novel Hierarchical Nanoparticle Reduces Proinflammatory Cytokine Levels in Prostate Cancer Cells.Cancers · 2025Article
- Notch signaling in cancers: mechanism and potential therapy.Frontiers in cell and developmental biology · 2025Review
- SRCAP is involved in porcine reproductive and respiratory syndrome virus activated Notch signaling pathway.Journal of virology · 2024Article
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Prostate cancer stem cells and their targeted therapies.Frontiers in cell and developmental biology · 2024Review
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- Polysaccharides from Lentinus edodes prevent acquired drug resistance to docetaxel in prostate cancer cells by decreasing the TGF-β1 secretion of cancer-associated fibroblasts.Journal of natural medicines · 2023Article
- The roles of proteases in prostate cancer.IUBMB life · 2023Review
- The Molecular Biology of Prostate Cancer Stem Cells: From the Past to the Future.International journal of molecular sciences · 2023Review
- Review
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.International journal of biological sciences · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
Corrections and comments
- Commented on by
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
purposeTo investigate the efficacy and mechanisms of Notch signaling inhibition as an adjuvant to docetaxel in castration-resistant prostate cancer (CRPC) using a γ-secretase inhibitor (GSI), PF-03084014. EXPERIMENTAL
designThe effect of PF-03084014 on response to docetaxel was evaluated in docetaxel-sensitive and docetaxel-resistant CRPC cell lines in vitro and in murine models. Both soft tissue and bone sites were evaluated in vivo. Impacts on cell proliferation, apoptosis, cancer stem cells, and angiogenesis were evaluated.
resultsThe combination of PF-03084014 plus docetaxel reduced both docetaxel-sensitive and docetaxel-resistant CRPC tumor growth in soft tissue and bone greater than either agent alone. Antitumor activity was associated with PF-03084014-induced inhibition of Notch pathway signaling; decreased survival signals (cyclin E; MEK/ERK, PI3K/AKT, EGFR and NF-κB pathway; BCL-2, BCL-XL); increased apoptotic signals (BAK, BAX; cleaved caspase-3); reduced microvessel density; reduced epithelial-mesenchymal transition; and reduced cancer stem-like cells in the tumor.
conclusionsThese results reveal that PF-03084014 enhances docetaxel-mediated tumor response and provides a rationale to explore GSIs as adjunct therapy in conjunction with docetaxel for men with CRPC.
Indexed as
Identifiers
What OpenQuestion holds
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.