ArticleCancer discovery2017
A Unified Approach to Targeting the Lysosome's Degradative and Growth Signaling Roles.
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Article in Cancer discovery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
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143citing papers in PubMed, 1 pooled it
13.8field-weighted citation impact, top 1% of its field
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Who cites it
143 citing papers in PubMed, 1 synthesis or guideline pooled it, 200 citations in OpenAlex.
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer.The oncologist · 2023Trial
- BAMM (BRAF Autophagy and MEK Inhibition in Melanoma): A Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine in Advanced BRAFV600-mutant Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Drugging small-molecule compounds in autophagy-dependent cell death to overcome cancer therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Hepatic control of immunometabolism: implications for the pathogenesis, diagnosis and treatment of rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- The Role of Autophagy in Cancer Evolution and Prognosis, Highlighting Its Role in PCa and Its Interaction with Apoptosis and Epigenetic Regulation by miRNAs.Medical sciences (Basel, Switzerland) · 2026Review
- Dual targeting of SLC6A14 and autophagy/macropinocytosis enhances therapeutic efficacy in pancreatic ductal adenocarcinoma.The Biochemical journal · 2026Article
- Palmitic Acid Promotes Antiviral Innate Immunity via ZDHHC20-Mediated CMPK2 Palmitoylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ZDHHC9 palmitoylates LAMTOR1 to promote renal cell carcinoma malignant progression.Cell death & disease · 2026Article
- Autophagy Modulation in Cancer Immunotherapy, Emerging Molecular Targets and Drug Selection Strategies.International journal of molecular sciences · 2026Review
- Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.Cell communication and signaling : CCS · 2026Review
- Hepatocyte Autophagy in Malaria: Current Concepts, Emerging Mechanisms, and Future Therapeutic Directions.Pathogens (Basel, Switzerland) · 2026Review
- Regulated cell death in ovarian cancer: molecular mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- Lysosomal-stress-driven cargo-fate switching between autophagic degradation and small extracellular vesicle release in triple-negative breast cancer: a hypothesis and theory article.Frontiers in oncology · 2026Article
- Baicalin chemosensitivity enhancement of cisplatin in bladder cancer via autophagy flux inhibition.Frontiers in pharmacology · 2026Article
- A review of autophagy in the pancreas: normal physiology and pathophysiology.Autophagy reports · 2026Review
- The Roles of ProteinCancer communications (London, England) · 2026Review
- From "lysosomal addiction" to targeted therapies: exploiting novel windows in colorectal cancer.European journal of medical research · 2025Review
- Gut Metabolite Indole-3-Propionic Acid Regulates Macrophage Autophagy Through PPT1 Inhibiting Aging-Related Myocardial Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 7 institutions in 1 country.
Vito W RebeccaDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Michael C NicastriDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania.
Noel McLaughlinDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania.
Colin FennellyDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Quentin McAfeeDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Amruta RongheMolecular and Cellular Oncogenesis Program and Melanoma Research Center, Wistar Institute, Philadelphia, Pennsylvania.
Michel NofalDepartment of Chemistry and Integrative Genomics, Princeton University, Princeton, New Jersey.
Chun-Yan LimDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California.
Eric WitzeDepartment of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
Cynthia I ChudeDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Gao ZhangMolecular and Cellular Oncogenesis Program and Melanoma Research Center, Wistar Institute, Philadelphia, Pennsylvania.
Gretchen M AliceaMolecular and Cellular Oncogenesis Program and Melanoma Research Center, Wistar Institute, Philadelphia, Pennsylvania.
Shengfu PiaoDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Sengottuvelan MuruganDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Rani OjhaDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Samuel M LeviDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania.
Zhi WeiDepartment of Computer Science, New Jersey Institute of Technology, Newark, New Jersey.
Julie S Barber-RotenbergDepartment of Biochemistry and Biophysics, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
Maureen E MurphyMolecular and Cellular Oncogenesis Program and Melanoma Research Center, Wistar Institute, Philadelphia, Pennsylvania.
Gordon B MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Yiling LuDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Joshua RabinowitzDepartment of Chemistry and Integrative Genomics, Princeton University, Princeton, New Jersey.
Ronen MarmorsteinDepartment of Biochemistry and Biophysics, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
Qin LiuMolecular and Cellular Oncogenesis Program and Melanoma Research Center, Wistar Institute, Philadelphia, Pennsylvania.
Shujing LiuDepartment of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania.
Xiaowei XuDepartment of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania.
Meenhard HerlynMolecular and Cellular Oncogenesis Program and Melanoma Research Center, Wistar Institute, Philadelphia, Pennsylvania.
Roberto ZoncuDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California.
Donita C BradyDepartment of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
David W SpeicherMolecular and Cellular Oncogenesis Program and Melanoma Research Center, Wistar Institute, Philadelphia, Pennsylvania.
Jeffrey D WinklerDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania. ravi.amaravadi@uphs.upenn.edu winkler@sas.upenn.edu.
Ravi K AmaravadiDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. ravi.amaravadi@uphs.upenn.edu winkler@sas.upenn.edu.
University of Pennsylvania · USThe Wistar Institute · USPrinceton University · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, Berkeley · USUPMC Hillman Cancer Center · USNew Jersey Institute of Technology · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MUNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3MTumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9MTargeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F, WEERARATNA, ASHANI T · 2008 to 2023
$37.1M Tissue &PathologyP50CA093372 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2001 to 2009
$15.4MTargeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1MThe ARF Tumor SuppressorR01CA139319 · NCI · WISTAR INSTITUTE · PI MURPHY, MAUREEN E. · 2010 to 2019
$3.9MENGINEERING ORGANELLE FUNCTION TO REWIRE CANCER CELL METABOLISMDP2CA195761 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI ZONCU, ROBERTO · 2014 to 2014
$2.4MMolecular mechanisms of BRAF inhibitor induced UPR and autophagyR01CA198015 · NCI · UNIVERSITY OF PENNSYLVANIA · PI AMARAVADI, RAVI K · 2015 to 2019
$1.8MHLTF gene silencing: a novel determinant of sensitivity to autophagy inhibitionR01CA169134 · NCI · UNIVERSITY OF PENNSYLVANIA · PI AMARAVADI, RAVI K · 2013 to 2017
$1.7MRelationships Between Autoimmune IgG1 and IgG4 Repertoires in Pemphigus VulgarisF30AR065870 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI MUKHERJEE, ERIC MILAN · 2014 to 2016
$105kNCI NIH HHS DP2 CA195761NCI NIH HHS P01 CA114046NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA016520NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA093372NCI NIH HHS P50 CA174523NCI NIH HHS R01 CA139319NCI NIH HHS R01 CA169134NCI NIH HHS R01 CA198015
Abstract
Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e., autophagy and macropinocytosis) while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQ) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy. Central nitrogen methylation of the DQ linker enhances lysosomal localization and potency. An
Indexed as
AnimalsAntimalarialsAntineoplastic AgentsAutophagyCell Line, TumorCell ProliferationChloroquineHumansLysosomesMechanistic Target of Rapamycin Complex 1MelanomaMembrane ProteinsMiceMolecular Targeted TherapyProteolysisSignal TransductionAntimalarialsAntineoplastic AgentsChloroquineMechanistic Target of Rapamycin Complex 1Membrane ProteinsMTOR protein, humanPPT1 protein, humanThiolester HydrolasesTOR Serine-Threonine Kinases
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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.