{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:18:17Z","timestamp":1790698697886,"version":"4.1.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Molecular profiling (MP) and next-generation sequencing (NGS) have expanded the diagnostics evaluation of cancer by enabling genomic characterization that informs diagnosis and treatment selection. As the second leading cause of global mortality, cancer claimed nearly 10 million lives in 2020. Artificial intelligence (AI)-powered MP is increasingly recognized for its precision in diagnosing complex cancers, particularly cancers of unknown primary (CUP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report a case of a 69-year-old male with a history of treated prostate cancer, initially diagnosed with CUP and suspected pancreaticobiliary malignancy. Conventional diagnostics, including imaging and immunohistochemistry, failed to identify the primary tumor, leading to ineffective therapies. AI-powered MP (Molecular Intelligence) revealed an 82% likelihood of renal cell carcinoma (RCC), prompting a targeted biopsy that confirmed RCC with sarcomatoid differentiation, enabling effective treatment with pembrolizumab and axitinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This case highlights the potential role of AI-powered MP in resolving diagnostic uncertainty in CUP, where traditional methods like imaging and tumor markers are inconclusive. By identifying actionable biomarkers, MP facilitates personalized therapy, improving clinical outcomes. Further research is needed to validate the broader clinical utility of AI-driven MP as a decision-support tool for precision oncology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1664264","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:33:13Z","timestamp":1774416793000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The role of AI-powered molecular profiling in the diagnosis and management of cancers of unknown primary: a case report and literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Abdullah","family":"Esmail","sequence":"first","affiliation":[{"name":"Section of Gastrointestinal Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Hassanain","sequence":"additional","affiliation":[{"name":"Section of Gastrointestinal Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Xiu","sequence":"additional","affiliation":[{"name":"Charles W. Duncan Jr. Department of Medicine, Caris Life Sciences","place":["Phoenix, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maen","family":"Abdelrahim","sequence":"additional","affiliation":[{"name":"Section of Gastrointestinal Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital","place":["Houston, TX, United States"]},{"name":"Faculty of Medicine, The University of Jordan","place":["Amman, Jordan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","article-title":"Global Cancer Statistics 2022: the trends projection analysis","volume":"10","author":"Chhikara","year":"2023","journal-title":"Chem Biol Lett"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13293","article-title":"Multi-omic analysis in carcinoma of unknown primary (CUP): therapeutic impact of knowing the 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