Gautam, MridulKumar, Chethana D.Ramachandran, PournamiKumar, AviralGopalsamy, Indresh K.Swaminathan, GuruprasadhCordani, MarcoDinesh Kumar, Lekha2026-02-202026-02-202026-12-04Gautam, M., Kumar, C.D., Ramachandran, P., Kumar, A., Gopalsamy, I.K., Swaminathan, G., Cordani, M., & Kumar, L.D. (2026). Shifting tides from non-targeted chemotherapy to targeted therapies and small RNA-based bio drugs: A changing paradigm in cancer therapy. European Journal of Pharmacology, 1011, 178446. https://doi.org/10.1016/j.ejphar.2025.1784460014-299910.1016/j.ejphar.2025.178446https://hdl.handle.net/20.500.14352/132783Funding: LDK and Team were supported by CSIR-CCMB in-house funds. M.C. is supported by grant RYC2021-031003-I funded by MICIU/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR. Acknowledgement: We thank Dr. V Dinesh Kumar for editing and reviewing the manuscript. Authors are grateful to the Director, CCMB, Dr. Vinay Kumar Nandicoori for his support. We would like to thank Dr. Britny Blaize for her initial contribution in compiling clinical trial data Table 1. Declaration of competing interest: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Marco Cordani reports a relationship with OCA Global that includes consulting or advisory. Marco Cordani reports a relationship with EQA Certificados that includes consulting or advisory. Marco Cordani reports a relationship with Elsevier B.V. that includes board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Ever since its discovery in the early 20th century, chemotherapy has been the mainstream therapy for almost all cancers. Though several cycles of chemotherapy significantly reduce the proliferation and spread of the disease, they cause deleterious side effects. The adverse effects on the immune system imposed by these non-specific cytotoxic chemo drugs forced scientists to focus and give importance to boosting the immune system with a series of specific biological therapies. Stimulating or modulating the immune system to recognize and strike cancer cells (immunotherapy), combining with the application of gene knock down through RNA interference (RNAi) have spearheaded the cancer biotherapies, propelling them towards a more targeted and efficacious therapy regimen. Immunotherapy uses drugs like monoclonal antibodies, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cell therapy to enhance the immune response. These immune-based therapies can improve the specificity of cancer targeting and overcome immune evasion mechanisms employed by cancer cells. Further, soon after RNAi discovery, efforts have been made to adopt RNAi for its clinical applications in treating cancer. Different non-coding RNAs (ncRNAs) exert a distinct influence on gene expression and its regulation, offering a diversified toolkit for manipulating cellular pathways in the fight against cancer. This review article summarizes the currently used chemo drugs and their adverse effects and the shift of focus towards small RNA based bio-drugs as future cancer therapeutics.engAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/journal articlehttps://doi.org/10.1016/j.ejphar.2025.178446open access615.277.4:616-006.04Bio drugsChemotherapyClinical trialsImmunotherapyMonoclonal antibodiesRna-InterferencencRnasOncologíaFarmacología (Medicina)2390 Química Farmacéutica3201.01 Oncología