ArticleAutophagy2014
Development of potent autophagy inhibitors that sensitize oncogenic BRAF V600E mutant melanoma tumor cells to vemurafenib.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 106 citations in OpenAlex.
- 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
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Baicalin chemosensitivity enhancement of cisplatin in bladder cancer via autophagy flux inhibition.Frontiers in pharmacology · 2026Article
- METTL3-dependent mAutophagy · 2025Article
- Autophagy in cancer and protein conformational disorders.FEBS letters · 2025Review
- The role of non-coding RNAs in the regulation of cell death pathways in melanoma.Discover oncology · 2025Review
- Cell Death Modalities in Therapy of Melanoma.International journal of molecular sciences · 2025Review
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Review
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Synergistic induction of autophagy in gastric cancer by targeting CDK4/6 and MEK through AMPK/mTOR pathway.Heliyon · 2024Article
- The roles of cancer stem cells and therapeutic implications in melanoma.Frontiers in immunology · 2024Review
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions.International journal of molecular sciences · 2023Review
- The Cytoprotective Role of Autophagy in Response to BRAF-Targeted Therapies.International journal of molecular sciences · 2023Review
- Subversion of autophagy machinery and organelle-specific autophagy by SARS-CoV-2 and coronaviruses.Autophagy · 2023Review
- Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics.International journal of biological sciences · 2023Review
- Dieckol Inhibits Autophagic Flux and Induces Apoptotic Cell Death in A375 Human Melanoma Cells via Lysosomal Dysfunction and Mitochondrial Membrane Impairment.International journal of molecular sciences · 2022Article
- Exploring Amodiaquine's Repurposing Potential in Breast Cancer Treatment-Assessment of In-Vitro Efficacy & Mechanism of Action.International journal of molecular sciences · 2022Article
- The Histone Deacetylase Inhibitor ITF2357 (Givinostat) Targets Oncogenic BRAF in Melanoma Cells and Promotes a Switch from Pro-Survival Autophagy to Apoptosis.Biomedicines · 2022Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Autophagy is a dynamic cell survival mechanism by which a double-membrane vesicle, or autophagosome, sequesters portions of the cytosol for delivery to the lysosome for recycling. This process can be inhibited using the antimalarial agent chloroquine (CQ), which impairs lysosomal function and prevents autophagosome turnover. Despite its activity, CQ is a relatively inadequate inhibitor that requires high concentrations to disrupt autophagy, highlighting the need for improved small molecules. To address this, we screened a panel of antimalarial agents for autophagy inhibition and chemically synthesized a novel series of acridine and tetrahydroacridine derivatives. Structure-activity relationship studies of the acridine ring led to the discovery of VATG-027 as a potent autophagy inhibitor with a high cytotoxicity profile. In contrast, the tetrahydroacridine VATG-032 showed remarkably little cytotoxicity while still maintaining autophagy inhibition activity, suggesting that both compounds act as autophagy inhibitors with differential effects on cell viability. Further, knockdown of autophagy-related genes showed no effect on cell viability, demonstrating that the ability to inhibit autophagy is separate from the compound cytotoxicity profiles. Next, we determined that both inhibitors function through lysosomal deacidification mechanisms and ultimately disrupt autophagosome turnover. To evaluate the genetic context in which these lysosomotropic inhibitors may be effective, they were tested in patient-derived melanoma cell lines driven by oncogenic BRAF (v-raf murine sarcoma viral oncogene homolog B). We discovered that both inhibitors sensitized melanoma cells to the BRAF V600E inhibitor vemurafenib. Overall, these autophagy inhibitors provide a means to effectively block autophagy and have the potential to sensitize mutant BRAF melanomas to first-line therapies.
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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.