ArticleAutophagy2014
Phase I clinical trial and pharmacodynamic evaluation of combination hydroxychloroquine and doxorubicin treatment in pet dogs treated for spontaneously occurring lymphoma.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.
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
107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 162 citations in OpenAlex.
- Pooled it
- Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors.International journal of molecular sciences · 2017Pooled it
- Safety and Biologic Response of Pre-operative Autophagy Inhibition in Combination with Gemcitabine in Patients with Pancreatic Adenocarcinoma.Annals of surgical oncology · 2015Trial
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- LC3B as a potential serum biomarker for screening high-risk neuroblastoma patients.Acta neurologica Belgica · 2026Article
- Leveraging Dog Models to Uncover Human Cancer Insights.Research square · 2026Article
- Autophagy-Targeting Nanomedicine: Strike at the Heart of the Cancer via Precise Modulation of Autophagy.Exploration (Beijing, China) · 2025Review
- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Targeting selective autophagy and beyond: From underlying mechanisms to potential therapies.Journal of advanced research · 2024Review
- Bringing the Genomic Revolution to Comparative Oncology: Human and Dog Cancers.Annual review of biomedical data science · 2024Review
- Enhancing Therapeutic Efficacy in Cancer Treatment: Integrating Nanomedicine with Autophagy Inhibition Strategies.ACS omega · 2024Review
- SLC34A2 promotes cell proliferation by activating STX17-mediated autophagy in esophageal squamous cell carcinoma.Thoracic cancer · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Sensitivity of osteosarcoma cell lines to autophagy inhibition as determined by pharmacologic and genetic manipulation.Veterinary and comparative oncology · 2023Article
- Review of Canine Lymphoma Treated with Chemotherapy-Outcomes and Prognostic Factors.Veterinary sciences · 2023Review
- Autophagic mechanisms in longevity intervention: role of natural active compounds.Expert reviews in molecular medicine · 2023Review
- A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs.Frontiers in immunology · 2023Review
- Crosstalk between autophagy and immune cell infiltration in the tumor microenvironment.Frontiers in medicine · 2023Review
- Inhibition of autophagy; an opportunity for the treatment of cancer resistance.Frontiers in cell and developmental biology · 2023Review
47 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
6 authors at 4 institutions in 1 country.
Funding
Abstract
Autophagy is a lysosomal degradation process that may act as a mechanism of survival in a variety of cancers. While pharmacologic inhibition of autophagy with hydroxychloroquine (HCQ) is currently being explored in human clinical trials, it has never been evaluated in canine cancers. Non-Hodgkin lymphoma (NHL) is one of the most prevalent tumor types in dogs and has similar pathogenesis and response to treatment as human NHL. Clinical trials in canine patients are conducted in the same way as in human patients, thus, to determine a maximum dose of HCQ that can be combined with a standard chemotherapy, a Phase I, single arm, dose escalation trial was conducted in dogs with spontaneous NHL presenting as patients to an academic, tertiary-care veterinary teaching hospital. HCQ was administered daily by mouth throughout the trial, beginning 72 h prior to doxorubicin (DOX), which was given intravenously on a 21-d cycle. Peripheral blood mononuclear cells and biopsies were collected before and 3 d after HCQ treatment and assessed for autophagy inhibition and HCQ concentration. A total of 30 patients were enrolled in the trial. HCQ alone was well tolerated with only mild lethargy and gastrointestinal-related adverse events. The overall response rate (ORR) for dogs with lymphoma was 93.3%, with median progression-free interval (PFI) of 5 mo. Pharmacokinetic analysis revealed a 100-fold increase in HCQ in tumors compared with plasma. There was a trend that supported therapy-induced increase in LC3-II (the cleaved and lipidated form of microtubule-associated protein 1 light chain 3/LC3, which serves as a maker for autophagosomes) and SQSTM1/p62 (sequestosome 1) after treatment. The superior ORR and comparable PFI to single-agent DOX provide strong support for further evaluation via randomized, placebo-controlled trials in canine and human NHL.
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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.