Evidence map›Paper›PMID 40221400›Full record

ArticleCell death discovery2025

Sotorasib-impaired degradation of NEU1 contributes to cardiac injury by inhibiting AKT signaling.

Mengting Cheng, Wentong Wu, Qing Li, Xinyu Tao, Feng Jiang, Jinjin Li, Nonger Shen, Fei Wang, Peihua Luo, Qiaojun He and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

13 authors.

Mengting ChengClinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Wentong WuCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Qing LiClinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Xinyu TaoSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Feng JiangCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Jinjin LiCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Nonger ShenClinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Fei WangOutpatient Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Peihua LuoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Qiaojun HeCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Ping HuangClinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.ORCID http://orcid.org/0000-0003-1775-029X
Zhifei XuCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. xzfzjut@zju.edu.cn.ORCID http://orcid.org/0000-0002-1896-097X
Yiwen ZhangClinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China. zhangyiwen@hmc.edu.cn.

Funding

Chinese Medicine Research Program of Zhejiang Province 2022ZB017National Natural Science Foundation of China (National Science Foundation of China) NSFC-VR 82161138019Support Program for Longyuan Youth and Fundamental Research Funds for the Universities of Gansu Province (Support Program for Longyuan Youth) 226-203-00151
6 · The paper itself

Abstract

Sotorasib, the inaugural targeted inhibitor sanctioned for the management of patients afflicted with locally advanced or metastatic non-small cell lung cancer presenting the KRAS G12C mutation, has encountered clinical application constraints due to its potential for cardiac injury as evidenced by safety trials. This investigation has elucidated that the heightened expression of neuraminidase-1 (NEU1) constitutes the principal etiology of cardiac damage induced by sotorasib. Mechanistically, sotorasib treatment inhibited the ubiquitinated degradation of NEU1, leading to its elevated expression, which induced downstream AKT signaling pathway inhibition and mitochondrial dysfunction leading to cardiomyocyte apoptosis. Meanwhile, in vivo and in vitro studies showed that D-pantothenic acid (D-PAC) alleviated sotorasib-induced cardiac damage by promoting NEU1 degradation. In conclusion, this study revealed that NEU1 is a key protein in sotorasib cardiotoxicity and that reducing the level of this protein is a critical strategy for the clinical treatment of sotorasib-induced cardiac injury. Schematic representation of a mechanism.

Identifiers

PMID40221400
PMCPMC11993734

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Registered trials

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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.