Trial reportInternational journal of cancer2016
Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750-an antisense oligonucleotide against eIF4E-in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer.
Trial report in International journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01675128 (A Phase I/II Study of ISIS 183750 in Combination With Irinotecan in Irinotecan-refractory Colorectal Cancer), which is not on this map. Cited by 42 papers.
What it found
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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 Phase I/II Study of ISIS 183750 in Combination With Irinotecan in Irinotecan-refractory Colorectal Cancer
Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
- N7-Methylguanosine Modification in Colorectal Cancer: Molecular Insights and Clinical Implications.International journal of molecular sciences · 2026Review
- From ribosomopathies to therapeutic targets: ribosomal alterations in pediatric leukemogenesis and tumorigenesis.Frontiers in oncology · 2026Review
- RNA-binding proteins as therapeutic targets in cancer.RNA biology · 2025Review
- RNA-binding protein quaking: a multifunctional regulator in tumour progression.Annals of medicine · 2025Review
- Review
- Review
- The role of RNA binding proteins in cancer biology: A focus on FMRP.Genes & diseases · 2025Review
- Gene expression silencing therapy in tumors, focus on gastrointestinal and genitourinary tumors.Frontiers in immunology · 2025Review
- Advancing cancer treatments: The role of oligonucleotide-based therapies in driving progress.Molecular therapy. Nucleic acids · 2024Review
- Plasma growth factors maintain constitutive translation in platelets to regulate reactivity and thrombotic potential.Blood advances · 2024Article
- Surmounting Cancer Drug Resistance: New Perspective on RNA-Binding Proteins.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Identification of a First-in-Class Small-Molecule Inhibitor of the EIF4E-RBM38 Complex That Enhances Wild-type TP53 Protein Translation for Tumor Growth Suppression.Molecular cancer therapeutics · 2023Article
- Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors.International journal of molecular sciences · 2023Review
- Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer.World journal of gastroenterology · 2023Review
- N7-methylguanosine modification: from regulatory roles to therapeutic implications in cancer.American journal of cancer research · 2023Review
- Biological functions and research progress of eIF4E.Frontiers in oncology · 2023Review
- RNA binding proteins (RBPs) and their role in DNA damage and radiation response in cancer.Advanced drug delivery reviews · 2022Review
- Transcript-Targeted Therapy Based on RNA Interference and Antisense Oligonucleotides: Current Applications and Novel Molecular Targets.International journal of molecular sciences · 2022Review
- RNA-binding protein ZCCHC4 promotes human cancer chemoresistance by disrupting DNA-damage-induced apoptosis.Signal transduction and targeted therapy · 2022Article
- A Review: PI3K/AKT/mTOR Signaling Pathway and Its Regulated Eukaryotic Translation Initiation Factors May Be a Potential Therapeutic Target in Esophageal Squamous Cell Carcinoma.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
The eukaryotic translation initiation factor 4E (eIF4E) is a potent oncogene that is found to be dysregulated in 30% of human cancer, including colorectal carcinogenesis (CRC). ISIS 183750 is a second-generation antisense oligonucleotide (ASO) designed to inhibit the production of the eIF4E protein. In preclinical studies we found that EIF4e ASOs reduced expression of EIF4e mRNA and inhibited proliferation of colorectal carcinoma cells. An additive antiproliferative effect was observed in combination with irinotecan. We then performed a clinical trial evaluating this combination in patients with refractory cancer. No dose-limiting toxicities were seen but based on pharmacokinetic data and tolerability the dose of irinotecan was reduced to 160 mg/m(2) biweekly. Efficacy was evaluated in 15 patients with irinotecan-refractory colorectal cancer. The median time of disease control was 22.1 weeks. After ISIS 183750 treatment, peripheral blood levels of eIF4E mRNA were decreased in 13 of 19 patients. Matched pre- and posttreatment tumor biopsies showed decreased eIF4E mRNA levels in five of nine patients. In tumor tissue, the intracellular and stromal presence of ISIS 183750 was detected by IHC in all biopsied patients. Although there were no objective responses stable disease was seen in seven of 15 (47%) patients who were progressing before study entry, six of whom were stable at the time of the week 16 CT scan. We were also able to confirm through mandatory pre- and posttherapy tumor biopsies penetration of the ASO into the site of metastasis.
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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.