ArticleCell reports2021
ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells.
Article in Cell reports, 2021. 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, 17 citations in OpenAlex.
- Small-molecule binding-site discovery using silyl ether-enabled chemoproteomics.Nature chemistry · 2026Article
- ABL kinase inactivation induces transcription-replication conflicts and impairs replication fork progression in metastatic small cell lung cancer.Cell reports · 2026Article
- Lipophilic Statins Deplete GPX4 to Promote Ferroptosis and Sensitize Cancer Cells to Immune Checkpoint Blockade.Molecular cancer therapeutics · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Statins in the context of precision cancer medicine: important factors to consider.Medical oncology (Northwood, London, England) · 2025Review
- Metabolic adaptations of brain metastasis.Nature reviews. Cancer · 2025Review
- Statins as potential adjuvant therapy in lung cancer: a narrative review.Journal of thoracic disease · 2025Review
- Advances and challenges in human 3D solid tumor models.Advanced functional materials · 2025Article
- Cancer brain metastasis: molecular mechanisms and therapeutic strategies.Molecular biomedicine · 2025Review
- Screening andAnti-cancer agents in medicinal chemistry · 2025Article
- Article
- Paradoxical effects of statins on endothelial and cancer cells: the impact of concentrations.Cancer cell international · 2023Review
- Low-Dose Atorvastatin has Promoting Effect on Melanoma Tumor Growth and Angiogenesis in Mouse Model.Advanced biomedical research · 2023Article
- Association between Statin Use and Survival in Cancer Patients with Brain Metastasis: Retrospective Analysis from the Chinese Population.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- Effect of Statins on Lung Cancer Molecular Pathways: A Possible Therapeutic Role.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Cholesterol-Lowering Phytochemicals: Targeting the Mevalonate Pathway for Anticancer Interventions.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Targeting mitochondrial metabolism has emerged as a treatment option for cancer patients. The ABL tyrosine kinases promote metastasis, and enhanced ABL signaling is associated with a poor prognosis in lung adenocarcinoma patients. Here we show that ABL kinase allosteric inhibitors impair mitochondrial integrity and decrease oxidative phosphorylation. To identify metabolic vulnerabilities that enhance this phenotype, we utilized a CRISPR/Cas9 loss-of-function screen and identified HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway and target of statin therapies, as a top-scoring sensitizer to ABL inhibition. Combination treatment with ABL allosteric inhibitors and statins decreases metastatic lung cancer cell survival in vitro in a synergistic manner. Notably, combination therapy in mouse models of lung cancer brain metastasis and therapy resistance impairs metastatic colonization with a concomitant increase in animal survival. Thus, metabolic combination therapy might be effective to decrease metastatic outgrowth, leading to increased survival for lung cancer patients with advanced disease.
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Registered trials
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