Evidence map›Paper›PMID 36457011›Full record

ArticleCancer cell international2022

HDACs/mTOR inhibitor synergizes with pyrotinib in HER2-positive pancreatic cancer through degradation of mutant P53.

Tiebo Mao, Xiaofei Zhang, Haiyan Xu, Xiao Zhang, Weiyu Ge, Shumin Li, Jingyu Ma, Ming Yue, Shengbai Xue, Jiujie Cui and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 44% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Tiebo MaoState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Xiaofei ZhangState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Haiyan XuState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Xiao ZhangState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Weiyu GeState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Shumin LiState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Jingyu MaState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Ming YueState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Shengbai XueState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Jiujie CuiState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China.
Liwei WangState Key Laboratory of Oncogenes and Related GenesDepartment of OncologySchool of Medicine, Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University, Shanghai, China. liweiwang@shsmu.edu.cn.
Shanghai Jiao Tong University · CNRenji Hospital · CNState Key Laboratory of Oncogene and Related Genes · CN

Funding

Clinical Research Plan of SHDC SHDC2020CR1035BFostering Fund of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine PYIV-17-001Innovation Group Project of Shanghai Municipal Health Commission 2019CXJQ03National Natural Science Foundation of China 81874048National Natural Science Foundation of China 82171824Project from CSCO Clinical Oncology Research Foundation Y-2019AZZD-0513Scientific and Technological Innovation Project of Science and Technology Commission of Shanghai Munici-pality 21JC1404300Shanghai Municipal Commission of Health and Family Planning 2018ZHYL0223Shanghai Municipal Commission of Health and Family Planning Grant 2018ZHYL0223
6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma (PDAC), as a highly lethal malignancy with high mortality, lacks of effective treatment. Canonical therapeutic targets in PDAC demand further verification among which HER2 receptor tyrosine kinase inhibitor pyrotinib as treatment targets has not be decided.

methodsAnti-PDAC efficacy of pyrotinib was evaluated both in vitro and in vivo using both cell lines and patient-derived xenografts. By screening a large-scale library of 1453 compounds, we identified HDACs/mTOR inhibitor 1 as a promising candidate to synergize with pyrotinib. The combination therapy was evaluated in vitro and in vivo in multiple cell lines and animal models. Furthermore, RNA-seq analysis was performed to reveal the latent molecular mechanism of combination therapy.

resultsIn our study, pyrotinib monotherapy was found to be inefficient to anti-PDAC which exhibited limited anti-proliferation effect in vitro and in vivo. Through therapy combined with HDACs/mTOR inhibitor 1, pyrotinib triggered intense apoptosis in PDAC both in cell lines and animal models. Mechanistic analyses revealed that mutant P53 degradation mediated by HDAC inhibition synergized with HER2 and mTOR inhibition.

conclusionsIn conclusion, identification of HDACs/mTOR inhibitor as a synergistic inhibitor, provides a potent therapeutic strategy that targets HER2-positive pancreatic cancer.

Indexed as

ApoptosisHDACHER2mTORPancreatic ductal adenocarcinomaPyrotinib

Identifiers

PMID36457011
PMCPMC9714091
OpenAlexW4310530784

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.