ArticleOncotarget2017
Drug-dependent functionalization of wild-type and mutant p53 in cisplatin-resistant human ovarian tumor cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed.
- The Enigmatic Tumor Suppressor p53 Biomolecule: Its Role and Prognostic and Predictive Values in Cancer Therapy and Precision Medicine.Biomolecules · 2026Review
- Profiling the Preclinical Pharmacokinetics and Biodistribution of a Platinum(IV)-Based Oxaliplatin Prodrug OxaliTEX and Their Significance to Antitumor Response.Molecular pharmaceutics · 2025Article
- Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.Journal of ovarian research · 2025Review
- Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions.Discover oncology · 2024Review
- Extracellular vesicles of Bifidobacterium longum reverse the acquired carboplatin resistance in ovarian cancer cells via p53 phosphorylation on Ser15.The Kaohsiung journal of medical sciences · 2024Article
- Expression of human dCTP pyrophosphatase 1 (DCTPP1) and its association with cisplatin resistance characteristics in ovarian cancer.Journal of cellular and molecular medicine · 2024Article
- Aberrant MAPK Signaling Offers Therapeutic Potential for Treatment of Ovarian Carcinoma.OncoTargets and therapy · 2022Review
- Porphyrinoid Drug Conjugates.Chem · 2020Article
- Protein expression profiling identifies differential modulation of homologous recombination by platinum-based antitumor agents.Cancer chemotherapy and pharmacology · 2020Article
- Cisplatin in Combination with MDM2 Inhibition Downregulates Rad51 Recombinase in a Bimodal Manner to Inhibit Homologous Recombination and Augment Tumor Cell Kill.Molecular pharmacology · 2020Article
- Oxaliplatin Pt(IV) prodrugs conjugated to gadolinium-texaphyrin as potential antitumor agents.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Acylated Ghrelin Renders Chemosensitive Ovarian Cancer Cells Resistant to Cisplatin Chemotherapy via Activation of the PI3K/Akt/mTOR Survival Pathway.Analytical cellular pathology (Amsterdam) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Cisplatin (cis-Pt) resistance in tumor cells from p53 dysfunction is a significant clinical problem. Although mutation can inhibit p53 function, >60% of p53 mutants retain normal function according to literature reports. Therefore, we examined the status of p53 in cisplatin-resistant ovarian tumor models and its functional response to cis-Pt and the mechanistically-distinct non-cross-resistant oxaliplatin (oxali-Pt). Relative to sensitive A2780 cells harboring wild-type p53, the 2780CP/Cl-16, OVCAR-10, Hey and OVCA-433 cell lines were 10- to 30-fold resistant to cis-Pt, but was substantially circumvented by oxali-Pt. Mutant p53 in 2780CP/Cl-16 (p53V172F) and OVCAR-10 (p53V172F and p53G266R) cells, predicted as non-functional in p53 database, displayed attenuated response to cis-Pt, as did the polymorphic p53P72R (functionally equivalent to wild-type p53) in HEY and OVCA-433 cell lines. However, p53 was robustly activated by oxali-Pt in all cell lines, with resultant drug potency confirmed as p53-dependent by p53 knockout using CRISPR/Cas9 system. This p53 activation by oxali-Pt was associated with phosphorylation at Ser20 by MEK1/2 based on inhibitor and kinase studies. Cis-Pt, however, failed to phosphorylate Ser20 due to downregulated Chk2, and its clinical impact validated by reduced overall survival of ovarian cancer patients according to TCGA database. In conclusion, cis-Pt resistance occurs in both wild-type and mutant p53 ovarian cancer cells, but is associated with loss of Ser20 phosphorylation. However, these mutant p53, like polymorphic p53, are functional and activated by oxali-Pt-induced Ser20 phosphorylation. Thus, the potential exists for repurposing oxali-Pt or similar drugs against refractory cancers harboring wild-type or specific mutant p53.
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.