ArticleOncotarget2017
Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- The metabolic addiction of cancer stem cells.Frontiers in oncology · 2022Pooled it
- Adipose triglyceride lipase driven lipolysis as a targetable metabolic vulnerability in prostate cancer with intrinsic metabolic inflexibility.British journal of cancer · 2026Article
- Tributyltin Protumorigenic Effects Targeting Prostate Cancer Cell Metabolism, Proliferation, Migration, and Invasion.Environmental toxicology · 2026Article
- Rewired lipid metabolism in castration-resistant prostate cancer: molecular interplay between glucose metabolism and sterol synthesis.Molecular biology reports · 2026Review
- Reprogrammed Lipid Metabolism-Associated Therapeutic Vulnerabilities in Prostate Cancer.International journal of molecular sciences · 2025Review
- Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025Review
- Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to Therapeutic Innovation.International journal of molecular sciences · 2025Review
- The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer.Molecular cancer · 2025Article
- Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- Metabolic adaptations in prostate cancer.British journal of cancer · 2024Review
- Unlocking ferroptosis in prostate cancer - the road to novel therapies and imaging markers.Nature reviews. Urology · 2024Review
- Altered metabolism in cancer: insights into energy pathways and therapeutic targets.Molecular cancer · 2024Review
- CAVPENET Peptide Inhibits Prostate Cancer Cells Proliferation and Migration through PP1γ-Dependent Inhibition of AKT Signaling.Pharmaceutics · 2024Article
- Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy.Pharmaceutics · 2024Review
- Fatty acid oxidation is critical for the tumorigenic potential and chemoresistance of pancreatic cancer stem cells.Journal of translational medicine · 2024Article
- Sterile inflammation via TRPM8 RNA-dependent TLR3-NF-kB/IRF3 activation promotes antitumor immunity in prostate cancer.The EMBO journal · 2024Article
- Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies.Cell communication and signaling : CCS · 2024Review
- New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance.ACS central science · 2023Article
- Perhexiline: Old Drug, New Tricks? A Summary of Its Anti-Cancer Effects.Molecules (Basel, Switzerland) · 2023Review
- Targeting lipid metabolism in metastatic prostate cancer.Therapeutic advances in medical oncology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0.001) especially in those with high-grade tumors. Since lipid oxidation is stimulated by androgens, we have evaluated the synergistic effects of combining CPT1A inhibition and anti-androgen therapy. Mechanistically, we have found that decreased CPT1A expression is associated with decreased AKT content and activation, likely driven by a breakdown of membrane phospholipids and activation of the INPP5K phosphatase. This results in increased androgen receptor (AR) action and increased sensitivity to the anti-androgen enzalutamide. To better understand the clinical implications of these findings, we have evaluated fat oxidation inhibitors (etomoxir, ranolazine and perhexiline) in combination with enzalutamide in PCa cell models. We have observed a robust growth inhibitory effect of the combinations, including in enzalutamide-resistant cells and mouse TRAMPC1 cells, a more neuroendocrine PCa model. Lastly, using a xenograft mouse model, we have observed decreased tumor growth with a systemic combination treatment of enzalutamide and ranolazine. In conclusion, our results show that improved anti-cancer efficacy can be achieved by co-targeting the AR axis and fat oxidation via CPT1A, which may have clinical implications, especially in the mCRPC setting.
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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.