ArticleAmerican journal of translational research2024
Neuroendocrine prostate cancer drivers SOX2 and BRN2 confer differential responses to imipridones ONC201, ONC206, and ONC212 in prostate cancer cell lines.
Article in American journal of translational research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed.
- Mitochondrial Protease ClpP: Cancer Marker and Drug Target.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Combination of the First-in-Class Imipridone ONC201 and Standard Anticancer Therapies as a Rational Approach for Therapeutic Benefit.Current issues in molecular biology · 2025Review
Corrections and comments
- Update of
Authors and funding
6 authors.
Funding
Abstract
objectivesProstate cancer (PCa) is a leading cause of cancer death in men worldwide. Approximately 30% of castrate-resistant PCa becomes refractory to therapy due to neuroendocrine differentiation (NED) that is present in <1% of de-novo tumors. First-in-class imipridone ONC201/TIC10 therapy has shown clinical activity against midline gliomas, neuroendocrine tumors, and PCa. We explored whether NED promotes sensitivity to imipridones ONC201 and ONC206 by inducibly overexpressing SOX2 and BRN2, well-known neuroendocrine drivers.
methodsInducible SOX2 or BRN2 systems were cloned into human PCa cell lines LNCaP and DU145. Inducible cell lines were characterized based on protein expression, morphology, and migration. The sensitivity of the inducible cell lines to imipridone therapy was determined by viability, cell growth, or clonogenic assays.
resultsSlight protection from ONC201 or ONC206 with SOX2 and BRN2 overexpression was observed in the inducible LNCaP cells but not in the DU145 cells. At 2 months, there was an apparent increase in CLpP expression in LNCaP SOX2-overexpressing cells, though this did not confer enhanced sensitivity to ONC201. DU145 SOX2-overexpressing cells had a significantly reduced ONC201 sensitivity than DU145 control cells.
conclusionsThe results suggest that treatment of castrate-resistant prostate cancer by imipridones may not be substantially affected by neuroendocrine differentiation as a therapy-resistance mechanism. The results support further testing of imipridones across subtypes of androgen-sensitive and castrate-resistant prostate cancer.
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.