ArticleJCI insight2019
Mitochondrial fusion exploits a therapeutic vulnerability of pancreatic cancer.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 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
114 citing papers in PubMed, 166 citations in OpenAlex.
- ZO-2 blocks the localization of PGAM5 protein to the mitochondrial membrane and suppresses pancreatic cancer malignancy through metabolic reprogramming.Genes & diseases · 2027Article
- Remodeling of mitochondrial dynamics by metabolic pathways couples to oncogenic growth inScience advances · 2026Article
- Reactivation of DRP1 plays a functional role in resistance to MEK inhibition in pancreatic cancer cells.British journal of cancer · 2026Article
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- CPT1A drives cisplatin resistance via acetylation‑dependent activation of DRP1 and mitochondrial fission in small cell lung cancer.Cell death & disease · 2026Article
- Reactivation of DRP1 plays a functional role in resistance to MEK inhibition in pancreatic cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Imbalances of mitochondrial dynamics in solid tumors.Oncogenesis · 2026Review
- Mitochondrial dynamics in neurodevelopment and neurodevelopmental disorders.Nature reviews. Neuroscience · 2026Review
- A novel mitochondrial-associated risk score reveals a potential link between pancreatic ductal adenocarcinoma and chemotherapy resistance as well as poor response to immunotherapy.Discover oncology · 2026Article
- Regulation of mitochondrial biogenesis and energy metabolism in the heart.Chinese medical journal · 2026Review
- Review
- Mitophagy in pancreatic cancer: mechanistic insights and implications for novel therapeutic strategies.Cell death discovery · 2026Review
- Targeting mitochondria as a potential therapeutic strategy against radioresistance in cancer.Frontiers in oncology · 2026Review
- Shared molecular mechanisms in aging and neurodegenerative diseases: from mechanistic insights to therapeutic strategies.Frontiers in human neuroscience · 2026Review
- Proteomics analysis reveals progesterone receptor induced mitochondria-mediated apoptosis in breast cancer cells.Scientific reports · 2025Article
- Article
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- Exposure to an environmentally relevant mixture of polychlorinated biphenyls affects mitochondrial bioenergetics and plasticity.Redox biology · 2025Article
- Defining the MYC-regulated transcriptome and kinome that support KRAS- and ERK-dependent growth of pancreatic cancer.Science signaling · 2025Article
- Targeting the MARCH5-MFN2 axis to enhance mitochondrial fusion and sensitize multiple myeloma cells to venetoclax.Journal of translational medicine · 2025Article
54 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
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) requires mitochondrial oxidative phosphorylation (OXPHOS) to fuel its growth, however, broadly inhibiting this pathway might also disrupt essential mitochondrial functions in normal tissues. PDAC cells exhibit abnormally fragmented mitochondria that are essential to its oncogenicity, but it was unclear if this mitochondrial feature was a valid therapeutic target. Here, we present evidence that normalizing the fragmented mitochondria of pancreatic cancer via the process of mitochondrial fusion reduces OXPHOS, which correlates with suppressed tumor growth and improved survival in preclinical models. Mitochondrial fusion was achieved by genetic or pharmacologic inhibition of dynamin related protein-1 (Drp1) or through overexpression of mitofusin-2 (Mfn2). Notably, we found that oral leflunomide, an FDA-approved arthritis drug, promoted a two-fold increase in Mfn2 expression in tumors and was repurposed as a chemotherapeutic agent, improving the median survival of mice with spontaneous tumors by 50% compared to vehicle. We found that the chief tumor suppressive mechanism of mitochondrial fusion was enhanced mitophagy, which proportionally reduced mitochondrial mass and ATP production. These data suggest that mitochondrial fusion is a specific and druggable regulator of pancreatic cancer growth that could be rapidly translated to the clinic.
Indexed as
Identifiers
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.