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Although the World Health Organization (WHO) three\u2010step analgesic ladder has substantially improved pain management, inadequate analgesia, opioid\u2010related adverse effects, and refractory pain continue to pose significant clinical challenges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This narrative review critically evaluates recent advances in cancer pain management, including novel analgesics, optimized opioid formulations, nanomedicine, invasive interventions (intrathecal drug delivery, neuromodulation, and neurolysis), and complementary integrative therapies, aiming to provide up\u2010to\u2010date insights for clinicians and researchers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Novel analgesics targeting \u03bc\u2010opioid receptor bias, ion channels, and multitarget strategies have shown preclinical promise. Improved opioid formulations and nanomedicine\u2010based approaches may enhance drug delivery and reduce toxicity. Fourth\u2010step interventions, including intrathecal drug delivery, neuromodulation, and neurolysis, provide targeted options for selected patients with refractory cancer pain. Integrative therapies, including mind\u2013body interventions, acupuncture, massage, music therapy, and game\u2010based approaches, may improve symptom burden and quality of life, although evidence for direct analgesic effects remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cancer pain management is evolving toward a multimodal and increasingly personalized framework. Despite substantial progress, many emerging therapies lack robust cancer\u2010specific validation. High\u2010quality clinical trials, standardized treatment protocols, and improved translational strategies are needed to establish evidence\u2010based precision cancer pain management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/prm\/5161889","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:19:28Z","timestamp":1785511168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breaking Through Cancer Pain: From Single\u2010Drug Management to Multimodal Analgesia"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3985-335X","authenticated-orcid":false,"given":"Yating","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3819-8699","authenticated-orcid":false,"given":"Shu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4064-1693","authenticated-orcid":false,"given":"Bo","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8735-7560","authenticated-orcid":false,"given":"Zefeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-312X","authenticated-orcid":false,"given":"He","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6910-8824","authenticated-orcid":false,"given":"Jing","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.18.2476"},{"key":"e_1_2_12_2_2","first-page":"1","article-title":"Intrathecal Drug Delivery Systems for Cancer Pain: A Health Technology Assessment","volume":"24","author":"Ontario Health","year":"2024","journal-title":"Ont Health Technol Assess Ser"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.4103\/ijpc.ijpc_277_20"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/papr.13098"},{"key":"e_1_2_12_5_2","first-page":"93","article-title":"WHO Guidelines for the Use of Analgesics in Cancer Pain","volume":"7","author":"Ventafridda V.","year":"1985","journal-title":"International Journal of Tissue Reactions"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1142\/s0192415x24500058"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14081992"},{"key":"e_1_2_12_8_2","first-page":"1111","article-title":"Treatment of Cancer Pain: Role of Neural Blockade and Neuromodulation","author":"Burton A. 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