{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:13:39Z","timestamp":1786115619338,"version":"build-2736575974"},"reference-count":162,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02ycyys66","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>RNA-binding proteins (RBPs) remain underexplored as small-molecule targets, although their dysregulation contributes to numerous human diseases, including cancer. RBPs are key regulators of post-transcriptional gene expression, controlling multiple stages of RNA metabolism. Among them, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is an oncofetal RBP that is highly expressed during embryonic development, largely absent in adult tissues, and re-expressed in multiple malignancies. A growing body of evidence supports IGF2BP3 as a diagnostic and prognostic biomarker and a potent oncogenic driver across tumor types, underscoring its potential as a therapeutic target. However, the development of effective IGF2BP3-targeting compounds remains in its early stages. In this review, we first describe the structural organization of IGF2BP3, the molecular basis of RNA recognition, and the mechanisms underlying its dysregulation across human cancers. We then discuss emerging therapeutic approaches, including direct inhibition of IGF2BP3\u2013RNA interactions and indirect strategies that rewire IGF2BP3 expression or activity through epigenetic, epitranscriptomic, and signaling pathways. By critically highlighting the opportunities and limitations of these approaches and their impact on cancer progression, we provide an integrated perspective combining structural biology, medicinal chemistry, and cancer biology to support the development of next-generation IGF2BP3-targeted therapies.<\/jats:p>","DOI":"10.3390\/ijms27156992","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:15:22Z","timestamp":1785834922000},"page":"6992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting IGF2BP3 in Cancer: From Molecular Structure and Biology to Early Drug Discovery"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-2532","authenticated-orcid":false,"given":"Elisa","family":"Uliassi","sequence":"first","affiliation":[{"name":"Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum\u2013Universit\u00e0 di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1289-5361","authenticated-orcid":false,"given":"Maria Laura","family":"Bolognesi","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum\u2013Universit\u00e0 di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6114-9499","authenticated-orcid":false,"given":"Katia","family":"Scotlandi","sequence":"additional","affiliation":[{"name":"Laboratory of Oncology Research and Functional Genomics (ONCOGEN), IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5778-4251","authenticated-orcid":false,"given":"Caterina","family":"Mancarella","sequence":"additional","affiliation":[{"name":"Laboratory of Oncology Research and Functional Genomics (ONCOGEN), IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2025.2470511","article-title":"RNA-binding proteins as therapeutic targets in cancer","volume":"22","author":"Jungfleisch","year":"2025","journal-title":"RNA Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1038\/s41467-019-10523-3","article-title":"Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia","volume":"10","author":"Minuesa","year":"2019","journal-title":"Nat. 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