ArticleAutophagy2014
Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
188 citing papers in PubMed, 2 syntheses or guidelines pooled it, 285 citations in OpenAlex.
- Antimalarials may reduce cancer risk in patients with systemic lupus erythematosus: a systematic review and meta-analysis of prospective studies.Annals of medicine · 2021Pooled 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
- Trial
- Autophagy Modulation in Cancer Therapy: Navigating the Dual Roles to Overcome Chemoresistance.Health science reports · 2026Article
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- p97 Inhibition Synergistically Enhances Hypomethylating Therapy through Targeting of PLK1 in Acute Myeloid Leukemia.Cancer research communications · 2026Article
- Deciphering autophagy-metabolism interactions in cancer drug resistance: a comprehensive review.Cancer chemotherapy and pharmacology · 2026Review
- Photocaged Chloroquine Derivatives for the Light-Dependent Inhibition of Autophagy in Cancer Stem Cells.ACS chemical biology · 2026Article
- Annexin A1 triggers autophagy to orchestrate radioiodine resistance in thyroid cancer via upregulating HMGB1.Cancer cell international · 2026Article
- The multifaceted functions of selective autophagy in cancer: molecular basis, consequences, and clinical prospects.Molecular cancer · 2026Review
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Article
- Inhibiting autophagy enhances anti-cancer properties of sulforaphane.Scientific reports · 2026Article
- The Expendables: Overlooked Medications with Anti-Cancer Properties.Current oncology reports · 2025Review
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- Autophagy in cancer and protein conformational disorders.FEBS letters · 2025Review
- The dual role of autophagy in cancer stem cells: implications for tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- REDD1 is a determinant of the sensitivity of renal cell carcinoma cells to autophagy inhibition that can be therapeutically exploited by targeting PIM activity.Cancer letters · 2025Article
128 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
We previously reported that inhibition of autophagy significantly augmented the anticancer activity of the histone deacetylase (HDAC) inhibitor vorinostat (VOR) through a cathepsin D-mediated mechanism. We thus conducted a first-in-human study to investigate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and VOR in patients with advanced solid tumors. Of 27 patients treated in the study, 24 were considered fully evaluable for study assessments and toxicity. Patients were treated orally with escalating doses of HCQ daily (QD) (d 2 to 21 of a 21-d cycle) in combination with 400 mg VOR QD (d one to 21). Treatment-related adverse events (AE) included grade 1 to 2 nausea, diarrhea, fatigue, weight loss, anemia, and elevated creatinine. Grade 3 fatigue and/or myelosuppression were observed in a minority of patients. Fatigue and gastrointestinal AE were dose-limiting toxicities. Six-hundred milligrams HCQ and 400 mg VOR was established as the maximum tolerated dose and recommended phase II regimen. One patient with renal cell carcinoma had a confirmed durable partial response and 2 patients with colorectal cancer had prolonged stable disease. The addition of HCQ did not significantly impact the PK profile of VOR. Treatment-related increases in the expression of CDKN1A and CTSD were more pronounced in tumor biopsies than peripheral blood mononuclear cells. Based on the safety and preliminary efficacy of this combination, additional clinical studies are currently being planned to further investigate autophagy inhibition as a new approach to increase the efficacy of HDAC inhibitors.
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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.