# Emerging trends and knowledge networks in pan-cancer sorafenib resistance: a 20-year bibliometric investigation

## TL;DR

This paper analyzes 20 years of research on sorafenib resistance across cancers, identifying key mechanisms and future strategies to improve treatment outcomes.

## Contribution

A novel bibliometric analysis of sorafenib resistance across multiple cancers, revealing interdisciplinary trends and a conceptual framework for overcoming resistance.

## Key findings

- 1,484 publications on sorafenib resistance were analyzed, with a peak in 2022 and a focus on hepatocellular carcinoma.
- Key resistance mechanisms include drug transporters, metabolic reprogramming, and tumor microenvironment interactions.
- Future strategies include nanoparticle delivery systems, combination therapies, and multi-omics data mining.

## Abstract

Sorafenib, a multi-kinase inhibitor, is a key therapeutic agent in the treatment of advanced hepatocellular carcinoma (HCC), metastatic renal cell carcinoma (RCC), and radioactive iodine-refractory differentiated thyroid cancer (DTC). However, its clinical efficacy is frequently hampered by the rising prevalence of sorafenib resistance, particularly in HCC. This reality underscores the urgent need for a comprehensive pan-cancer investigation to elucidate the underlying mechanisms of resistance.

We employed a systematic bibliometric approach utilizing the Web of Science Core Collection to conduct a structured literature search. Performance analysis and visualization were conducted using VOSviewer and CiteSpace. A triphasic screening protocol was implemented to identify publications focused on sorafenib resistance, covering a period from 2006 to 2025.

Our analysis identified 1,484 eligible publications, with a peak of 194 articles published in 2022. The majority of research (79.48%) centered on HCC, with significant contributions from institutions in China and the United States. Co-authorship and keyword network analyses revealed a robust interdisciplinary collaboration landscape. Key themes emerged, including dysregulation of drug transporters and clearance mechanisms, metabolic reprogramming, programmed cell death, interactions within the tumor microenvironment, and epigenetic regulatory mechanisms, highlighting critical areas contributing to resistance.

This study highlights the current research landscape concerning sorafenib resistance, facilitating the identification of emerging trends and research gaps. Future research priorities should include biomarker-driven clinical trials, the development of nanoparticle delivery systems, and the clinical translation of combination therapy strategies. Additionally, the integration of deep learning algorithms in the context of big data has the potential to enhance our understanding of resistance mechanisms in silico, ultimately aiming to overcome resistance challenges and improve patient survival outcomes.

Knowledge Framework of Sorafenib Resistance: Mechanisms and Future Directions This three-layered conceptual map synthesizes 20 years of research on sorafenib resistance across cancers: Core (Central Circle): Sorafenib Resistance — The focal theme of this bibliometric analysis, reflecting its pan-cancer clinical challenge; Intermediate Layer (Mechanisms): Six key resistance drivers identified through literature mining; Outer Layer (Solutions): Emerging strategies to overcome resistance.Diagram illustrating factors influencing sorafenib resistance, divided into sections: Combination Therapy, Translational Medicine, Clinical Trials, Nanoparticle Delivery Systems, and Multi-omics Data Mining. Each section contains related concepts, such as metabolic reprogramming, tumor microenvironment, programmed cell death, pharmacokinetics, and epigenetic regulation, represented with icons.

Knowledge Framework of Sorafenib Resistance: Mechanisms and Future Directions This three-layered conceptual map synthesizes 20 years of research on sorafenib resistance across cancers: Core (Central Circle): Sorafenib Resistance — The focal theme of this bibliometric analysis, reflecting its pan-cancer clinical challenge; Intermediate Layer (Mechanisms): Six key resistance drivers identified through literature mining; Outer Layer (Solutions): Emerging strategies to overcome resistance.