ReviewMedical oncology (Northwood, London, England)2020
NUC-1031, use of ProTide technology to circumvent gemcitabine resistance: current status in clinical trials.
Review in Medical oncology (Northwood, London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Stereoselective Synthesis of Nucleotide Analog Prodrugs (ProTides) via an Oxazaphospholidine Method.The Journal of organic chemistry · 2025Article
- 2'-Fluorinated nucleoside chemistry for new drug discovery: achievements and prospects.National science review · 2024Review
- Cytotoxicity of phosphoramidate, bis-amidate and cycloSal prodrug metabolites against tumour and normal cells.RSC medicinal chemistry · 2024Article
- Advanced prodrug strategies in nucleoside analogues targeting the treatment of gastrointestinal malignancies.Frontiers in cell and developmental biology · 2023Review
- Review
- Expanding the toolbox of metabolically stable lipid prodrug strategies.Frontiers in pharmacology · 2022Article
- Moving forward in the treatment of cholangiocarcinoma.World journal of gastrointestinal oncology · 2021Review
- The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance MechanismsClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08).The oncologist · 2021Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance to gemcitabine chemotherapy is common in patients with pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC) and ovarian cancers (OC), conferring poor survival. Use of ProTide technology led to the development of a 'partially-activated' monophosphorylated gemcitabine compound, termed NUC-1031. NUC-1031 enters cancer cells independent of the human equilibrative nucleoside transporter, does not require deoxycytidine kinase-mediated activation and resists cytidine deaminase-mediated breakdown into toxic by-products. CURRENT
findingsThe phase I PRO-001 trial recruited 68 patients with advanced solid tumours; of the 49 patients that had response-evaluable disease, 5 (10%) had a partial response (PR) and 33 (67%) had stable disease (SD). Subsequently, the PRO-002 study assessed the safety and efficacy of NUC-1031 combined with carboplatin for patients with OC (n = 25); preliminary data from this study reported one (4%) unconfirmed complete response (CR), 8 (35%) PRs and 13 (57%) patients with SD, the final outcome data are awaited. The ABC-08 trial for advanced BTC assessed safety and efficacy of NUC-1031 combined with cisplatin; 14 patients were recruited with a 50% objective response rate in the intention to treat population at interim analysis. ACELARATE, the phase III trial in first-line advanced PDAC comparing NUC-1031 to gemcitabine monotherapy, recruited 200 patients but has been paused for futility analysis.
conclusionEarly studies demonstrate NUC-1031 is well tolerated with favourable pharmacokinetic profiles. NUC-1031 use in PDAC remains unclear, but encouraging results of disease control in BTC and OC has prompted phase II and III trial development. NuTide 121, is a phase III trial comparing cisplatin-NUC 1031 combination to the standard of care cisplatin-gemcitabine and recruitment is ongoing. Recruiting trials and mature data from existing studies will help inform on the impact of NUC-1031 on patient survival over standard gemcitabine.
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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.