ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 119 papers, 1 of them a synthesis that pooled it.
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Who cites it
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 236 citations in OpenAlex.
- Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors.International journal of molecular sciences · 2017Pooled it
- A Phase II Study of the Efficacy and Safety of Chloroquine in Combination With Taxanes in the Treatment of Patients With Advanced or Metastatic Anthracycline-refractory Breast Cancer.Clinical breast cancer · 2021Trial
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.Immunology · 2026Review
- MinimalRSC chemical biology · 2026Article
- Tumor Lipidomic Changes after Treatment with Polymeric Hydroxychloroquine in a Syngeneic Murine Model of Pancreatic Cancer.ACS omega · 2026Article
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Targeting autophagy and metabolism for ewing sarcoma.Molecular biology reports · 2025Review
- Distinct mechanisms of cell in breast cancer and their clinical implication.Cell biology and toxicology · 2025Review
- Autophagy-Targeting Nanomedicine: Strike at the Heart of the Cancer via Precise Modulation of Autophagy.Exploration (Beijing, China) · 2025Review
- Research Advances of the Autophagy-Regulated Radiosensitivity.Cell proliferation · 2025Review
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- Autophagy: The convergence point of aging and cancer.Biochemistry and biophysics reports · 2025Review
- Structure-Activity Relationship Studies of an Autophagy Inhibitor That Targets the ATG14L-Beclin1 Protein-Protein Interaction Reveal Modifications That Improve Potency and Solubility and Maintain Selectivity.Journal of medicinal chemistry · 2025Article
- Lysosome targeted therapies in hematological malignancies.Frontiers in oncology · 2025Review
- Targeting Autophagy and the Anticipatory Unfolded Protein Response Leads to Increased Breast Cancer Cell Death.microPublication biology · 2025Article
- Harnessing Drug Repurposing to Combat Breast Cancer by Targeting Altered Metabolism and Epithelial-to-Mesenchymal Transition Pathways.ACS pharmacology & translational science · 2024Review
- Malignancy in systemic lupus erythematosus: relation to disease characteristics in 92 patients - a single center retrospective study.Rheumatology international · 2024Article
- Endoplasmic reticulum stress-a key guardian in cancer.Cell death discovery · 2024Review
- Complex Interplay between DNA Damage and Autophagy in Disease and Therapy.Biomolecules · 2024Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
purposeEstrogen receptor-α (ERα)-targeted therapies including tamoxifen (TAM) or Faslodex (ICI) are used to treat ER(+) breast cancers. Up to 50% of tumors will acquire resistance to these interventions. Autophagy has been implicated as a major driver of antiestrogen resistance. We have explored the ability of hydroxychloroquine (HCQ), which inhibits autophagy, to affect antiestrogen responsiveness. EXPERIMENTAL
designTAM-resistant MCF7-RR and ICI-resistant/TAM cross-resistant LCC9 ER(+) breast cancer cells were injected into mammary fat pads of female athymic mice and treated with TAM and/or ICI in combination with oral low-dose HCQ.
resultsWe show that HCQ can increase antiestrogen responsiveness in MCF7-RR and LCC9 cells and tumors, likely through the inhibition of autophagy. However, the combination of ICI+HCQ was less effective than HCQ alone in vivo, unlike the TAM+HCQ combination. Antiestrogen treatment stimulated angiogenesis in tumors but did not prevent HCQ effectiveness. The lower efficacy of ICI+HCQ was associated with ICI effects on cell-mediated immunity within the tumor microenvironment. The mouse chemokine KC (CXCL1) and IFNγ were differentially regulated by both TAM and ICI treatments, suggesting a possible effect on macrophage development/activity. Consistent with these observations, TAM+HCQ treatment increased tumor CD68(+) cells infiltration, whereas ICI and ICI+HCQ reduced peripheral tumor macrophage content. Moreover, macrophage elimination of breast cancer target cells in vitro was reduced following exposure to ICI.
conclusionHCQ restores antiestrogen sensitivity to resistant tumors. Moreover, the beneficial combination of TAM+HCQ suggests a positive outcome for ongoing neoadjuvant clinical trials using this combination for the treatment of ER(+) ductal carcinoma in situ lesions.
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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.