ArticleBritish journal of cancer2023
Inhibition of branched-chain alpha-keto acid dehydrogenase kinase augments the sensitivity of ovarian and breast cancer cells to paclitaxel.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Revealing the landscape of targeting mitochondrial functions and behaviors to overcome cancer chemoresistance.Journal of the National Cancer Center · 2025Review
- Protein lipoylation in cancer: metabolic reprogramming and therapeutic potential.Cell death discovery · 2025Review
- Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets.Journal of translational medicine · 2025Review
- Unveiling the Maze: Branched-Chain Amino Acids Fueling the Dynamics of Cancer Metabolism and Progression.Cancers · 2025Review
- Multiple roles of branched-chain amino acid metabolism in tumour progression.Journal of biomedical science · 2025Review
- Branched-Chain Amino Acid Catabolism Promotes Ovarian Cancer Cell Proliferation via Phosphorylation of mTOR.Cancer research communications · 2025Article
- BCAA metabolism in cancer progression and therapy resistance: The balance between fuel and cell signaling.Frontiers in pharmacology · 2025Review
- BCAA metabolism: the Achilles' heel of ovarian cancer, polycystic ovary syndrome, and premature ovarian failure.Frontiers in endocrinology · 2025Review
- Incretin-Based Therapies: A Promising Approach for Modulating Oxidative Stress and Insulin Resistance in Sarcopenia.Journal of bone metabolism · 2024Article
- Branched-chain amino acid catabolism promotes ovarian cancer cell proliferation via phosphorylation of mTOR.bioRxiv : the preprint server for biology · 2024Article
- Article
- MAZ-mediated up-regulation of BCKDK reprograms glucose metabolism and promotes growth by regulating glucose-6-phosphate dehydrogenase stability in triple-negative breast cancer.Cell death & disease · 2024Article
- Review
- Exploring the Interplay between Vitamin D, Insulin Resistance, Obesity and Skeletal Health.Journal of bone metabolism · 2024Article
- Impact of calcium channel blockers and angiotensin receptor blockers on hematological parameters in type 2 diabetic patients.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Branched-chain amino acids catabolism and cancer progression: focus on therapeutic interventions.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
contextMany cancer patients who initially respond to chemotherapy eventually develop chemoresistance, and to address this, we previously conducted a RNAi screen to identify genes contributing to resistance. One of the hits from the screen was branched-chain α-keto acid dehydrogenase kinase (BCKDK). BCKDK controls the metabolism of branched-chain amino acids (BCAAs) through phosphorylation and inactivation of the branched-chain α-keto acid dehydrogenase complex (BCKDH), thereby inhibiting catabolism of BCAAs.
methodsWe measured the impact on paclitaxel sensitivity of inhibiting BCKDK in ovarian and breast cancer cell lines.
resultsInhibition of BCKDK using siRNA or two chemical inhibitors (BCKDKi) was synergistic with paclitaxel in both breast and ovarian cancer cells. BCKDKi reduced levels of BCAA and the addition of exogenous BCAA suppressed this synergy. BCKDKi inactivated the mTORC1-Aurora pathway, allowing cells to overcame M-phase arrest induced by paclitaxel. In some cases, cells almost completed cytokinesis, then reverted to a single cell, resulting in multinucleate cells.
conclusionBCKDK is an attractive target to augment the sensitivity of cancer cells to paclitaxel.
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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 OpenQuestion graph.