Evidence map›Paper›PMID 42645178›Full record

ArticleCells2026

1D228 Attenuates Sorafenib Resistance in Renal Cell Carcinoma Models by Dual Targeting c-Met and AXL.

Hanxu Qian, Huimin Ren, Lei Xu, Xingge Hu, Yihong Sun, Qing Ju, Chenguo Zhang, Shuo Liu, Baijiao An, Chunhua Yang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Hanxu QianShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Huimin RenShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Lei XuShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Xingge HuShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Yihong SunShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Qing JuShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Chenguo ZhangShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Shuo LiuShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Baijiao AnShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.ORCID 0000-0001-7683-2389
Chunhua YangShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Xingjie LiuMedicine and Pharmacy Research Center, Shandong Medical and Pharmaceutical University, Yantai 264003, China.
Yin ZhangShandong Center of Technology Innovation for Molecular Targeting and Intelligent Diagnosis and Treatment, Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medical and Pharmaceutical University, Yantai 264003, China.ORCID 0000-0002-5591-645X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sorafenib is widely used to treat metastatic renal cell carcinoma (RCC); however, the acquired drug resistance limits its efficacy and application in clinical practice. The receptor tyrosine kinases c-Met and AXL play important roles in cancer progression and are involved in tyrosine kinase inhibitor-induced drug resistance in cancers, but whether these two receptors also contribute to sorafenib-induced drug resistance in RCC is unclear. In this study, we evaluated our synthesized compound 1D228, a TKI derived from Tepotinib, in sorafenib-resistant RCC models, which demonstrated further inhibition in sorafenib-resistant RCC cells, and induced 25% more reduction in resistant RCC tumor size by 1D228 combined with sorafenib compared with sorafenib monotherapy in animal models. Mechanistically, resistant RCC exhibited elevated phosphorylation of c-Met and AXL, which was effectively suppressed by 1D228. These findings indicated that compound 1D228 sensitized the sorafenib resistance of RCC by dual targeting the c-Met and AXL signaling pathways. This study suggests that 1D228 may represent a promising preclinical therapeutic strategy for RCC patients with sorafenib resistance mediated by c-Met and AXL activation.

Indexed as

Carcinoma, Renal CellDrug Resistance, NeoplasmKidney NeoplasmsProto-Oncogene ProteinsProto-Oncogene Proteins c-metReceptor Protein-Tyrosine KinasesSorafenibAnimalsAxl Receptor Tyrosine KinaseCell Line, TumorHumansMiceMice, NudePhosphorylationProtein Kinase InhibitorsSignal TransductionAXL protein, humanAxl Receptor Tyrosine KinaseProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins c-metReceptor Protein-Tyrosine KinasesSorafenib1D228AXLc-Metrenal cell carcinomasorafenib resistance

Identifiers

PMID42645178
PMCPMC13510577

What OpenQuestion holds

Textmetadata
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.