Trial reportJournal of cancer research and clinical oncology2011
RP101 (brivudine) binds to heat shock protein HSP27 (HSPB1) and enhances survival in animals and pancreatic cancer patients.
Trial report in Journal of cancer research and clinical oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00550004 (Randomized, Double Blind, Placebo Controlled, Phase 2 Study Evaluating the Efficacy & Safety of RP101 or Placebo in Combination With Gemcitabine Administered as First-Line Treatment to Subjects With Unresectable, Locally Advanced, or Metastatic Pancreatic Adenocarcinoma), which is not on this map. Cited by 51 papers.
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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.
Randomized, Double Blind, Placebo Controlled, Phase 2 Study Evaluating the Efficacy & Safety of RP101 or Placebo in Combination With Gemcitabine Administered as First-Line Treatment to Subjects With Unresectable, Locally Advanced, or Metastatic Pancreatic Adenocarcinoma
Who cites it
51 citing papers in PubMed, 102 citations in OpenAlex.
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Review
- Heat Shock Proteins in Pancreatic Cancer: Pathogenic Mechanisms and Clinical Implications.Cells · 2025Review
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Review
- Heat shock protein paradigms in cancer progression: future therapeutic perspectives.3 Biotech · 2024Review
- The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics.Cancers · 2024Review
- Impact of oseltamivir on the risk of cancer.Frontiers in oncology · 2024Article
- Crossroad between the Heat Shock Protein and Inflammation Pathway in Acquiring Drug Resistance: A Possible Target for Future Cancer Therapeutics.Biomedicines · 2023Review
- Intestinal Apc-inactivation induces HSP25 dependency.EMBO molecular medicine · 2022Article
- Activation of the HSP27-AKT axis contributes to gefitinib resistance in non-small cell lung cancer cells independent of EGFR mutations.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- The Role of Hsp27 in Chemotherapy Resistance.Biomedicines · 2022Review
- The Role of Heat Shock Protein 27 in Carcinogenesis and Treatment of Colorectal Cancer.Current pharmaceutical design · 2022Review
- Article
- Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer.Cancers · 2021Article
- Drug-Like Small Molecule HSP27 Functional Inhibitor Sensitizes Lung Cancer Cells to Gefitinib or Cisplatin by Inducing Altered Cross-Linked Hsp27 Dimers.Pharmaceutics · 2021Article
- Small Hsps as Therapeutic Targets of Cystic Fibrosis Transmembrane Conductance Regulator Protein.International journal of molecular sciences · 2021Review
- Chemical validation of a druggable site on Hsp27/HSPB1 using in silico solvent mapping and biophysical methods.Bioorganic & medicinal chemistry · 2021Article
- Life-long passion for antiviral research and drug development: 80th birthday of Prof. Dr. Erik De Clercq.Biochemical pharmacology · 2021Review
- AlphaB-crystallin and breast cancer: role and possible therapeutic strategies.Cell stress & chaperones · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral reports describe the importance of the chaperone HSP27 (HSPB1) in cancer progression, and the demand for drugs that modulate HSPB1-activity is increasing rapidly. We reported earlier that RP101 (Bromovinyldeoxyuridine, BVDU, Brivudine) improves the efficacy of chemotherapy in pancreatic cancer.
methodsChemistry: Binding of RP101 and HSPB1 was discovered by affinity chromatography. Molecular and cell biology: HSPB1 in vitro transcription/translation (TNT), Pull down using RP101-coupled magnetic beads, Immuno Co-precipitations, Structural modeling of HSP27 (HSPB1), Introduction of point mutations into linear expression templates by PCR, Heat shock, Tumor Invasion. Animal experiments: Treatment of AH13r Sarcomas in SD-rats. Clinical Studies with late-stage pancreatic cancer patients: Pilot study, Dose finding study, Phase II study (NCT00550004).
resultsHere, we report that RP101 binds in vitro to the heat shock protein HSPB1 and inhibits interaction with its binding partners. As a result, more activated CASP9 was detected in RP101-treated cancer cells. We modeled HSPB1-structure and identified the RP101 binding site. When we tested RP101 as an anti-cancer drug in a rat model, we found that it improved chemotherapy. In clinical studies with late-stage pancreatic cancer patients, the dose of 500 mg/day was safe and efficient, but 760 mg/day turned out to be too high for lightweight patients.
conclusionsThe development of RP101 as a cancer drug represents a truly novel approach for prevention of chemoresistance and enhancement of chemosensitivity.
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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.