{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:29:46Z","timestamp":1790623786528,"version":"4.1.0"},"reference-count":139,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Neuroendocrine neoplasms (NENs) are biologically diverse tumors. This article is a critical review of recent evidence focusing on systemic therapies (through mid-2025). We summarize what is most practice-relevant and where gaps remain. In diagnosis, somatostatin-receptor PET\/CT has largely replaced older scintigraphy, and adding FDG PET can flag more aggressive disease. Blood-based tests and selected tissue markers (e.g., MGMT, DAXX\/ATRX\/ALT) show promise but require cautious interpretation in routine care. In treatment, radioligand therapy (PRRT) is used earlier in appropriate receptor-positive disease; cabozantinib improves progression-free survival after prior therapy; and belzutifan offers a biomarker-guided option for malignant pheochromocytoma\/paraganglioma. Immunotherapy remains limited to defined subsets, including high-grade neoplasms. We appraise strengths and limitations of key trials, note issues of access and toxicity, and highlight active areas in development (SSTR antagonists, alpha emitters, and dose-guided PRRT). Our goal is to provide a concise, evidence-based map of the field to support informed clinical judgment and future research priorities.<\/jats:p>","DOI":"10.3390\/cancers17223632","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:56:47Z","timestamp":1762945007000},"page":"3632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Emerging Diagnostics and Therapies in Neuroendocrine Neoplasms: A Critical Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-6509","authenticated-orcid":false,"given":"Jorge H.","family":"Hernandez-Felix","sequence":"first","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-1113","authenticated-orcid":false,"given":"Monica Isabel","family":"Meneses-Medina","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0107-9617","authenticated-orcid":false,"given":"Rachel","family":"Riechelmann","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, AC Camargo Cancer Center, Rua Antonio Prudente 211, Sao Paulo 01509-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8405-218X","authenticated-orcid":false,"given":"Jonathan","family":"Strosberg","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3342-397X","authenticated-orcid":false,"given":"Rocio","family":"Garcia-Carbonero","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario 12 de Octubre, Imas12, Medicine Faculty, Universidad Complutense Madrid (UCM), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-4030","authenticated-orcid":false,"given":"Jaydira del","family":"Rivero","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19245","DOI":"10.18632\/oncotarget.24983","article-title":"Global burden of neuroendocrine tumors and changing incidence in Kentucky","volume":"9","author":"Chauhan","year":"2018","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2515798","DOI":"10.1001\/jamanetworkopen.2025.15798","article-title":"Epidemiology of Neuroendocrine Neoplasms in the US","volume":"8","author":"Dasari","year":"2025","journal-title":"JAMA Netw. 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