AUTHOR=Dong Jiayi , Su Ting , Wu Jiexiong , Xiang Yu , Song Minghan , He Canfeng , Shao Lijuan , Yang Yubin , Chen Size TITLE=Drug functional remapping: a new promise for tumor immunotherapy JOURNAL=Frontiers in Oncology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1519355 DOI=10.3389/fonc.2025.1519355 ISSN=2234-943X ABSTRACT=The research and development of new anti-cancer drugs face challenges such as high costs, lengthy development cycles, and limited data on side effects. In contrast, the clinical safety and side effects of traditional drugs have been well established through long-term use. The development or repurposing of traditional drugs with potential applications in cancer treatment offers an economical, feasible, and promising strategy for new drug development. This article reviews the novel applications of traditional drugs in tumor immunotherapy, discussing how they can enhance tumor treatment efficacy through functional repositioning, while also reducing development time and costs. Recent advancements in cancer immunotherapy have revolutionized treatment options, but resistance to ICIs remains a significant challenge. Drug repurposing has emerged as a promising strategy to identify novel agents that can enhance the efficacy of immunotherapies by overcoming ICI resistance. A study suggests that drug repositioning has the potential to modulate immune cell activity or alter the tumor microenvironment, thereby circumventing the resistance mechanisms associated with immune checkpoint blockade. This approach provides a rapid and cost-effective pathway for identifying therapeutic candidates that can be quickly transitioned into clinical trials. To improve the effectiveness of tumor immunotherapy, it is crucial to explore systematic methods for identifying repurposed drug candidates. Methods such as high-throughput screening, computational drug repositioning, and bioinformatic analysis have been employed to efficiently identify potential candidates for cancer treatment. Furthermore, leveraging databases related to immunotherapy and drug repurposing can provide valuable resources for drug discovery and facilitate the identification of promising compounds. It focuses on the latest advancements in the use of antidiabetic drugs, antihypertensive agents, weight-loss medications, antifungal agents, and antiviral drugs in tumor immunotherapy, examining their mechanisms of action, clinical application prospects, and associated challenges. In this context, our aim is to explore these strategies and highlight their potential for expanding the therapeutic options available for cancer immunotherapy, providing valuable references for cancer research and treatment.