{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T15:18:03Z","timestamp":1781363883986,"version":"3.54.1"},"reference-count":148,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH NCI","award":["R01CA240607"],"award-info":[{"award-number":["R01CA240607"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroendocrine tumors (NETs) are heterogeneous neoplasms with different molecular characteristics and prognosis. Although slow-growing, NETs are often diagnosed at an advanced stage. The treatment choice depends on primary site, extent, grade, growth rate, somatostatin receptor status, functional status, performance status, and comorbidities. Precise knowledge of the biological and molecular features of NETs has led to the development of novel therapies. Therapeutic options include somatostatin analogs, multi-targeted tyrosine kinase inhibitors (e.g., sunitinib), or mammalian targets of rapamycin (mTOR) inhibitors (e.g., everolimus), telotristat ethyl, chemotherapy, and peptide-receptor radionuclide therapy. Pivotal studies that led to approval, treatment-related adverse events, and safety concerns, as demonstrated in clinical trials and real-world clinical practice. Questions, such as the optimal timing, selection, and sequence of therapies, and biomarkers that predict response to the novel agents in an individual patient, remain to be answered. We propose a stepwise approach for the management of advanced Gastro-entero-pancreatic (GEP)-NETs that utilizes a multidisciplinary team of experts. Biomarkers may assist in both the diagnosis and post-treatment follow-up in patients with GEP-NETs. The next decade of research on GEP-NETs is promising and should provide new insights into the molecular underpinnings of this disease, therapy selection, and the sequencing of the available therapies, along with the potential role of AL in NET pharmacotherapy.<\/jats:p>","DOI":"10.3390\/ijms262211095","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:24:58Z","timestamp":1763375098000},"page":"11095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Update on Novel Pharmacotherapies for the Treatment of Neuroendocrine Tumors"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8145-3754","authenticated-orcid":false,"given":"Khalil","family":"Choucair","sequence":"first","affiliation":[{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R Street, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9276-3055","authenticated-orcid":false,"given":"Roupen","family":"Odabashian","sequence":"additional","affiliation":[{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R Street, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmita Nanja","family":"Reddy","sequence":"additional","affiliation":[{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R Street, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1178-9505","authenticated-orcid":false,"given":"Asfar Sohail","family":"Azmi","sequence":"additional","affiliation":[{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R Street, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8154-957X","authenticated-orcid":false,"given":"Muhammad Wasif","family":"Saif","sequence":"additional","affiliation":[{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R Street, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10555-011-9292-1","article-title":"Current knowledge on diagnosis and staging of neuroendocrine tumors","volume":"30","author":"Castellano","year":"2011","journal-title":"Cancer Metastasis Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/CEJ.0000000000000877","article-title":"Incidence trend of neuroendocrine tumors and disparities by sex and race\/ethnicity in adults from the United States, 2000\u20132020","volume":"33","author":"Zhu","year":"2024","journal-title":"Eur. 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