ArticleCancer cell2021
Cancer cells escape autophagy inhibition via NRF2-induced macropinocytosis.
Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
What it found
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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.
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Who cites it
121 citing papers in PubMed, 210 citations in OpenAlex.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- DHODH inhibition drives albumin-mediated drug resistance through TERF2IP lactylation-activated macropinosome-mitochondria contact.Nature communications · 2026Article
- Acquisition of Resistance to RAS Inhibition Is Associated with the Upregulation of Macropinocytosis through Both PI3K-Dependent and -Independent Signaling.Cancer research communications · 2026Article
- Pictilisib and nutrient stress synergize to induce methuosis via PI(4,5)PCell death & disease · 2026Article
- Arp2/3 complex and β1 integrin drive an invasive front through extracellular matrix adaptation in pancreatic cancer.International journal of cancer · 2026Article
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- Fatty acid scavenging enables cancer escape from KRAS inhibition.bioRxiv : the preprint server for biology · 2026Article
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- Smart Nanoparticles Disrupting Energy Supply through Triple Mechanisms to Kill Tumors via Dual Disruption of Mitochondria and Lysosomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Selective targeting of NRF2-high pancreatic ductal adenocarcinoma with an NQO1-activatable prodrug.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mitochondria and Aging: Redox Balance Modulation as a New Approach to the Development of Innovative Geroprotectors (Fundamental and Applied Aspects).International journal of molecular sciences · 2026Review
- KRAS-driven cytokine-metabolic crosstalk shapes immune exclusion in pancreatic ductal adenocarcinoma.Frontiers in genetics · 2026Review
- Targeting PIP5K ameliorates hepatic cancer by inhibiting PI3K/AKT and the autophagy mechanism and enhancing ROS-mediated apoptosis.Frontiers in pharmacology · 2026Article
- ATPase copper transporting beta contributes to cisplatin resistance as a regulatory factor of extracellular vesicles in head and neck squamous cell carcinoma.Cancer gene therapy · 2026Article
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- Targeting autophagy in dysfunctional tumor vasculature.iScience · 2025Review
- Tumour Cell Size Control and Its Impact on Tumour Cell Function.Cell proliferation · 2025Review
61 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
Many cancers, including pancreatic ductal adenocarcinoma (PDAC), depend on autophagy-mediated scavenging and recycling of intracellular macromolecules, suggesting that autophagy blockade should cause tumor starvation and regression. However, until now autophagy-inhibiting monotherapies have not demonstrated potent anti-cancer activity. We now show that autophagy blockade prompts established PDAC to upregulate and utilize an alternative nutrient procurement pathway: macropinocytosis (MP) that allows tumor cells to extract nutrients from extracellular sources and use them for energy generation. The autophagy to MP switch, which may be evolutionarily conserved and not cancer cell restricted, depends on activation of transcription factor NRF2 by the autophagy adaptor p62/SQSTM1. NRF2 activation by oncogenic mutations, hypoxia, and oxidative stress also results in MP upregulation. Inhibition of MP in autophagy-compromised PDAC elicits dramatic metabolic decline and regression of transplanted and autochthonous tumors, suggesting the therapeutic promise of combining autophagy and MP inhibitors in the clinic.
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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 Socratic graph.