ArticleEBioMedicine2016
Co-targeting hexokinase 2-mediated Warburg effect and ULK1-dependent autophagy suppresses tumor growth of PTEN- and TP53-deficiency-driven castration-resistant prostate cancer.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Targeting prostate adenocarcinoma tumor microenvironment via cancer nanotheranostics: a comprehensive update on improved roadmap for disease diagnosis, therapy and management.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Targeting RPS6KC1 to overcome enzalutamide resistance in prostate cancer.Biomarker research · 2025Article
- Targeting mitochondria and programmed cell death as potential interventions for metastatic castration-resistant prostate cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Article
- 2-Deoxyglucose and hydroxychloroquine HPLC-MS-MS analytical methods and pharmacokinetic interactions after oral co-administration in male rats.Pharmacology research & perspectives · 2024Article
- Repurposing Metabolic Inhibitors in the Treatment of Colon Adenocarcinoma Patient-Derived Models.Cells · 2023Article
- ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression.Military Medical Research · 2023Article
- Hexokinase 2 confers radio-resistance in hepatocellular carcinoma by promoting autophagy-dependent degradation of AIMP2.Cell death & disease · 2023Article
- Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer.Biomolecules · 2022Review
- Role of Glycolysis and Fatty Acid Synthesis in the Activation and T Cell-Modulating Potential of Dendritic Cells Stimulated with a TLR5-Ligand Allergen Fusion Protein.International journal of molecular sciences · 2022Article
- Exploiting the Metabolic Consequences of PTEN Loss and Akt/Hexokinase 2 Hyperactivation in Prostate Cancer: A New Role for δ-Tocotrienol.International journal of molecular sciences · 2022Article
- Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.Journal of experimental & clinical cancer research : CR · 2022Review
- Tumor Cell Glycolysis-At the Crossroad of Epithelial-Mesenchymal Transition and Autophagy.Cells · 2022Review
- Histone H2AX promotes metastatic progression by preserving glycolysis via hexokinase-2.Scientific reports · 2022Article
- Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.Pharmaceutics · 2022Review
- Construction of Glycolytic Regulator Gene Signature to Predict the Prognosis and Tumor Immune Cell Infiltration Levels for Prostate Cancer.Computational and mathematical methods in medicine · 2022Article
- Modulation of dendritic cell metabolism by an MPLA-adjuvanted allergen product for specific immunotherapy.Frontiers in immunology · 2022Article
- β-elemene Isopropanolamine Derivative LXX-8250 Induces Apoptosis Through Impairing Autophagic FluxFrontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Currently, no therapeutic options exist for castration-resistant prostate cancer (CRPC) patients who have developed resistance to the second generation anti-androgen receptor (AR) axis therapy. Here we report that co-deletion of Pten and p53 in murine prostate epithelium, often observed in human CRPC, leads to AR-independent CRPC and thus confers de novo resistance to second generation androgen deprivation therapy (ADT) in multiple independent yet complementary preclinical mouse models. In contrast, mechanism-driven co-targeting hexokinase 2 (HK2)-mediated Warburg effect with 2-deoxyglucose (2-DG) and ULK1-dependent autophagy with chloroquine (CQ) selectively kills cancer cells through intrinsic apoptosis to cause tumor regression in xenograft, leads to a near-complete tumor suppression and remarkably extends survival in Pten-/p53-deficiency-driven CRPC mouse model. Mechanistically, 2-DG causes AMPK phosphorylation, which in turn inhibits mTORC1-S6K1 translation signaling to preferentially block anti-apoptotic protein MCL-l synthesis to prime mitochondria-dependent apoptosis while simultaneously activates ULK1-driven autophagy for cell survival to counteract the apoptotic action of anti-Warburg effect. Accordingly, inhibition of autophagy with CQ sensitizes cancer cells to apoptosis upon 2-DG challenge. Given that 2-DG is recommended for phase II clinical trials for prostate cancer and CQ has been clinically used as an anti-malaria drug for many decades, the preclinical results from our proof-of-principle studies in vivo are imminently translatable to clinical trials to evaluate the therapeutic efficacy by the combination modality for a subset of currently incurable CRPC harboring PTEN and TP53 mutations.
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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.