Global Research Trends in Tyrosine Kinase Inhibitors: Coword and Visualization Study
Authors: Hu Jiming , Xing Kai , Zhang Yan , Liu Miao , Wang Zhiwei 
Published: January 2022

Background
Tyrosine kinase inhibitors (TKIs) have achieved revolutionary results in the treatment of a wide range of tumors, and many studies on this topic continue to be published every year. Some of the published reviews provide great value for us to understand TKIs. However, there is a lack of studies on the knowledge structure, bibliometric analysis, and visualization results in TKIs research.

Objective
This paper aims to investigate the knowledge structure, hotspots, and trends of evolution of the TKIs research by co-word analysis and literature visualization and help researchers in this field to gain a comprehensive understanding of the current status and trends.

Methods
We retrieved all academic papers about TKIs published between 2016 and 2020 from the Web of Science. By counting keywords from those papers, we generated the co-word networks by extracting the co-occurrence relationships between keywords, and then segmented communities to identify the subdirections of TKIs research by calculating the network metrics of the overall and local networks. We also mapped the association network topology, including the network within and between TKIs subdirections, to reveal the association and structure among varied subdirections. Furthermore, we detected keyword bursts by combining their burst weights and durations to reveal changes in the focus of TKIs research. Finally, evolution venation and strategic diagram were generated to reveal the trends of TKIs research.

Results
We obtained 6782 unique words (total frequency 26,175) from 5584 paper titles. Finally, 296 high-frequency words were selected with a threshold of 10 after discussion, the total frequency of which accounted for 65.41% (17,120/26,175). The analysis of burst disciplines revealed a variable number of burst words of TKIs research every year, especially in 2019 and 2020, such as HER2, pyrotinib, next-generation sequencing, immunotherapy, ALK-TKI, ALK rearrangement. By network calculation, the TKIs co-word network was divided into 6 communities: C1 (non-small–cell lung cancer), C2 (targeted therapy), C3 (chronic myeloid leukemia), C4 (HER2), C5 (pharmacokinetics), and C6 (ALK). The venation diagram revealed several clear and continuous evolution trends, such as non-small–cell lung cancer venation, chronic myeloid leukemia venation, renal cell carcinoma venation, chronic lymphocytic leukemia venation. In the strategic diagram, C1 (non-small–cell lung cancer) was the core direction located in the first quadrant, C2 (targeted therapy) was exactly at the junction of the first and fourth quadrants, which meant that C2 was developing; and C3 (chronic myeloid leukemia), C4 (HER2), and C5 (pharmacokinetics) were all immature and located in the third quadrant.

Conclusions
Using co-word analysis and literature visualization, we revealed the hotspots, knowledge structure, and trends of evolution of TKIs research between 2016 and 2020. TKIs research mainly focused on targeted therapies against varied tumors, particularly against non-small–cell lung cancer. The attention on chronic myeloid leukemia and pharmacokinetics was gradually decreasing, but the focus on HER2 and ALK was rapidly increasing. TKIs research had shown a clear development path: TKIs research was disease focused and revolved around “gene targets/targeted drugs/resistance mechanisms.” Our outcomes will provide sound and effective support to researchers, funders, policymakers, and clinicians.