{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:17:26Z","timestamp":1792282646460,"version":"4.4.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Small interfering RNA (siRNA) therapeutics have emerged as a promising class of nucleic acid-based medicines that selectively suppress the expression of disease-associated genes by targeting messenger RNAs (mRNAs). Unlike conventional small-molecule drugs and antibody therapeutics, which primarily act on proteins, siRNAs function at the mRNA level through the mechanism of RNA interference (RNAi), enabling selective silencing of targets that are difficult to address using traditional therapeutic approaches. Over the past decade, substantial advances in siRNA design, chemical modification, and delivery technologies have markedly improved the stability, efficacy, and safety of siRNA therapeutics. In particular, liver-targeted lipid nanoparticle (LNP) and N-acetylgalactosamine (GalNAc)-based delivery platforms have enabled the successful clinical translation of several siRNA drugs, leading to multiple regulatory approvals for the treatment of metabolic and rare genetic diseases. Despite these achievements, no siRNA-based therapeutic has yet been approved for cancer treatment. Oncology applications face several unique challenges, including efficient and selective delivery to tumor tissues, intratumoral heterogeneity, off-target effects, endosomal escape, and the complex tumor microenvironment. In this review, we summarize recent progress in siRNA therapeutics, with particular emphasis on oncology. We discuss the molecular basis of RNAi, clinical development in cancer, and key barriers limiting broader application. We also highlight emerging strategies, including mutation-specific siRNA approaches, that may enable more precise and personalized cancer therapies. Overcoming these challenges will be critical for expanding the clinical utility of siRNA therapeutics in oncology.<\/jats:p>","DOI":"10.1093\/jjco\/hyag099","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:47:23Z","timestamp":1781092043000},"page":"1189-1198","source":"Crossref","is-referenced-by-count":2,"title":["Progress in siRNA nucleic acid therapeutics and challenges in their application to cancer treatment"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-9025","authenticated-orcid":false,"given":"Kumiko","family":"Ui-Tei","sequence":"first","affiliation":[{"name":"NucleoTIDE and PepTIDE Drug Discovery Center, Institute of Biomedical Engineering, Institute of Science Tokyo , Tokyo 113-8519 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