Emerging research themes in drug resistance in osteosarcoma: a 25-year bibliometric and visualized analysis.

Abstract

Drug resistance is a major barrier to effective treatment in osteosarcoma, the most common primary malignant bone tumor in adolescents and young adults. Although advancements in surgical techniques and chemotherapeutic regimens have improved local control, long-term survival rates remain stagnant, largely due to intrinsic and acquired resistance mechanisms. This study aimed to perform a comprehensive bibliometric and visualized analysis of global research trends in osteosarcoma drug resistance from 2000 to 2025. A total of 927 English-language articles and reviews were retrieved from the Web of Science Core Collection and analyzed using VOSviewer, CiteSpace, Scimago Graphica, and Charticulator. Our findings reveal a steady increase in annual publications, with China and the USA leading in productivity and academic influence, respectively. Thematic evolution in this field has shifted from classical mechanisms such as P-glycoprotein and apoptosis to emerging areas including autophagy, EMT, non-coding RNAs, tumor microenvironment remodeling, and nanomedicine. Recent keyword and reference burst analyses suggest growing interest in immunotherapy, ferroptosis, metabolic vulnerabilities (e.g., methionine dependence), and exosome-mediated resistance pathways. This study provides a macroscopic view of the knowledge landscape in osteosarcoma drug resistance and highlights the importance of integrating interdisciplinary approaches such as spatial omics, immunometabolism, and precision drug delivery into future research and clinical translation. These insights may inform the development of novel and personalized therapeutic strategies to improve outcomes for osteosarcoma patients.