Evidence map›Paper›PMID 34319001›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021

RRM2 Regulates Sensitivity to Sunitinib and PD-1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway.

Wei Xiong, Bin Zhang, Haixin Yu, Liang Zhu, Lu Yi, Xin Jin

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 1 pooled it
18.6field-weighted citation impact, top 1% 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

106 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.

  1. Pooled it
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  12. Multi omics network toxicology andFrontiers in cell and developmental biology · 2026
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46 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Wei XiongDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Bin ZhangCancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Haixin YuCancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Liang ZhuDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Lu YiDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Xin JinDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.ORCID 0000-0001-6461-6005
Central South University · CNUnion Hospital · CN

Funding

National Natural Science Foundation of China 82073321
6 · The paper itself

Abstract

Renal cell carcinoma (RCC) is a malignant tumor of the kidneys. Approximately 70% of RCC cases are clear cell renal cell carcinoma with von Hippel-Lindau (VHL) gene mutation and activation of the vascular endothelial growth factor (VEGF) pathway. Tyrosine kinase inhibitors (TKIs) targeting VEGF have emerged as promising agents for RCC treatment. Apart from primary resistance, acquired resistance to TKIs after initial tumor regression is common in RCC. Recently, immune checkpoint inhibition, including PD-1/PD-L1 blockade, alone or in combination with TKIs has improved the overall survival of patients with RCC. Ribonucleotide reductase subunit M2 (RRM2) has been reported in many types of cancer and has been implicated in tumor progression. However, the role of RRM2 in TKIs resistance in RCC remains unclear. In this study, the authors have demonstrated that RRM2 is upregulated in sunitinib-resistant RCC cells and patient tissues. They also find that RRM2 stabilizes ANXA1 and activates the AKT pathway independent of its ribonucleotide reductase activity, promoting sunitinib resistance in RCC. Moreover, RRM2 regulated antitumor immune responses, and knockdown of RRM2 enhance the anti-tumor efficiency of PD-1 blockade in renal cancer. Collectively, these results suggest that aberrantly expressed RRM2 may be a promising therapeutic target for RCC.

Indexed as

Annexin A1Antineoplastic AgentsCell LineHumansImmune Checkpoint InhibitorsKidney NeoplasmsProto-Oncogene Proteins c-aktRibonucleoside Diphosphate ReductaseSignal TransductionSunitinibAnnexin A1Antineoplastic AgentsANXA1 protein, humanImmune Checkpoint InhibitorsProto-Oncogene Proteins c-aktRibonucleoside Diphosphate Reductaseribonucleotide reductase M2SunitinibANXA1PD-1 blockaderenal cell carcinomasRRM2tyrosine kinase inhibitors

Identifiers

PMID34319001
PMCPMC8456228
OpenAlexW3185428240

What OpenQuestion holds

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LicenceCC BY
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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.