ArticleCell death & disease2022
Lomitapide, a cholesterol-lowering drug, is an anticancer agent that induces autophagic cell death via inhibiting mTOR.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Therapeutic targeting of ROCK reverses EMT in lung cancer cells by impeding TAZ in Hippo signalling pathway.Molecular and cellular biochemistry · 2026Article
- Discovery of Lomitapide as a Novel Mast Cell Regulatory Agent Through Chemical Library Screening.European journal of immunology · 2026Article
- Crosstalk between NRP1 and autophagy in the tumor microenvironment: from molecular mechanisms to therapeutic targeting.Frontiers in immunology · 2026Review
- Adaptation to cystine limitation stress confers a targetable lipid metabolism vulnerability in pancreatic ductal adenocarcinoma.Nature communications · 2025Article
- A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: repurposing drugs to identify novel disruptors of 14-3-3 proteins.Cell death & disease · 2025Article
- Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity.Nature chemistry · 2025Article
- Integration of 101 machine learning algorithm combinations to unveil m6A/m1A/m5C/m7G-associated prognostic signature in colorectal cancer.Scientific reports · 2025Article
- X-linked ubiquitin-specific peptidase 11 (USP11) increases susceptibility to Cushing's disease in women.Acta neuropathologica communications · 2025Article
- Spatial genomics reveals cholesterol metabolism as a key factor in colorectal cancer immunotherapy resistance.Frontiers in oncology · 2025Article
- The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies.Metabolites · 2024Review
- Review
- Lipid-lowering drugs and cancer: an updated perspective.Pharmacological reports : PR · 2024Review
- StackER: a novel SMILES-based stacked approach for the accelerated and efficient discovery of ERα and ERβ antagonists.Scientific reports · 2023Article
- Revealing the role of epigenetic and post-translational modulations of autophagy proteins in the regulation of autophagy and cancer: a therapeutic approach.Molecular biology reports · 2023Review
- Present and Future of Dyslipidaemia Treatment-A Review.Journal of clinical medicine · 2023Review
- Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements-A Narrative Review.Nutrients · 2023Review
- The utility of 3D models to study cholesterol in cancer: Insights and future perspectives.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is a biological process that maintains cellular homeostasis and regulates the internal cellular environment. Hyperactivating autophagy to trigger cell death has been a suggested therapeutic strategy for cancer treatment. Mechanistic target of rapamycin (mTOR) is a crucial protein kinase that regulates autophagy; therefore, using a structure-based virtual screen analysis, we identified lomitapide, a cholesterol-lowering drug, as a potential mTOR complex 1 (mTORC1) inhibitor. Our results showed that lomitapide directly inhibits mTORC1 in vitro and induces autophagy-dependent cancer cell death by decreasing mTOR signaling, thereby inhibiting the downstream events associated with increased LC3 conversion in various cancer cells (e.g., HCT116 colorectal cancer cells) and tumor xenografts. Lomitapide also significantly suppresses the growth and viability along with elevated autophagy in patient-derived colorectal cancer organoids. Furthermore, a combination of lomitapide and immune checkpoint blocking antibodies synergistically inhibits tumor growth in murine MC38 or B16-F10 preclinical syngeneic tumor models. These results elucidate the direct, tumor-relevant immune-potentiating benefits of mTORC1 inhibition by lomitapide, which complement the current immune checkpoint blockade. This study highlights the potential repurposing of lomitapide as a new therapeutic option for cancer treatment.
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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.