ArticleOncotarget2017
ErbB2 inhibition by lapatinib promotes degradation of mutant p53 protein in cancer 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, 18 citations in OpenAlex.
- Antitumor Activities of Aqueous Cinnamon Extract on 5637 Cell Line of Bladder Cancer through Glycolytic Pathway.International journal of inflammation · 2022Article
- Resveratrol prevents hypoxia-induced retinal ganglion cell death related with ErbB2.International journal of ophthalmology · 2022Article
- The Polemic Diagnostic Role ofCancers · 2020Review
- Article
- Attenuation of p53 mutant as an approach for treatment Her2-positive cancer.Cell death discovery · 2020Review
- Interplay between HSF1 and p53 signaling pathways in cancer initiation and progression: non-oncogene and oncogene addiction.Cellular oncology (Dordrecht, Netherlands) · 2019Review
- Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.Oncotarget · 2018Article
- Heat shock factor 1 confers resistance to lapatinib in ERBB2-positive breast cancer cells.Cell death & disease · 2018Article
- p53 and metabolism: from mechanism to therapeutics.Oncotarget · 2018Review
- Correlation between osteosarcoma and the expression of WWOX and p53.Oncology letters · 2017Article
- Article
- Predicting the Efficacy of HER2-Targeted Therapies: A Look at the Host.Disease markers · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the p53 tumor suppressor gene are the most prevalent genetic events in human Her2-positive breast cancer and are associated with poor prognosis and survival. Human clinical data and our in vitro and in vivo studies strongly suggest potent oncogenic cooperation between mutant p53 and Her2 (ErbB2). Yet, the translational significance of mutant p53 in Her2 positive breast cancer, especially with respect to Her2-targeted therapies, has not been evaluated. Our previous work identified novel oncogenic activity of mutant p53 whereby mutp53 amplifies ErbB2 signaling via the mutp53-HSF1-ErbB2 feed-forward loop. Here we report that pharmacological interception of this circuit by ErbB2 inhibitor lapatinib downregulates mutant p53 in vitro and in vivo. We found that ErbB2 inhibition by lapatinib inhibits transcription factor HSF1, and its target Hsp90, followed by mutant p53 degradation in MDM2 dependent manner. Thus, our data suggest that mutant p53 sensitizes cancer cells to lapatinib via two complementary mechanisms: mutant p53 mediated amplification of ErbB2 signaling, and simultaneous annihilation of both potent oncogenic drivers, ErbB2 and mutant p53. Hence, our study could provide valuable information for the optimization of therapeutic protocols to achieve superior clinical effects in the treatment of Her2 positive breast 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.