{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:50:35Z","timestamp":1787590235621,"version":"build-2736575974"},"reference-count":112,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Foreign Affairs and International Cooperation\u200e","award":["VN21GR01\u200e"],"award-info":[{"award-number":["VN21GR01\u200e"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Despite the progress made in the diagnoses and therapy of gastrointestinal cancers, these diseases are still plagued by a high mortality. Thus, novel therapeutic approaches are urgently required. In this regard, small interfering RNA (siRNA), double-stranded RNA molecules able to specifically target the mRNA of pathological genes, have the potential to be of therapeutic value. To be effective in the human body, siRNAs need to be protected against degradation. Additionally, they need to target the tumor, leaving the normal tissue untouched in an effort to preserve organ function. To accomplish these tasks, siRNAs have been formulated with smart delivery systems such has polymers and lipids. While siRNA protection is not particularly difficult to achieve, their targeting of tumor cells remains problematic. Here, after introducing the general features of gastrointestinal cancers, we describe siRNA characteristics together with representative delivery systems developed for gastrointestinal cancers. Afterward, we present a selection of research papers employing siRNAs against upper- and lower- gastrointestinal cancers. For the liver, we also consider papers using siRNAs to combat liver cirrhosis, a relevant risk factor for liver cancer development. Finally, we present a brief description of clinical trials employing siRNAs for gastrointestinal cancers.<\/jats:p>","DOI":"10.3390\/ph15101295","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:34:30Z","timestamp":1666312470000},"page":"1295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Potential Application of Small Interfering RNA in Gastro-Intestinal Tumors"],"prefix":"10.3390","volume":"15","author":[{"given":"Pasquale","family":"Losurdo","sequence":"first","affiliation":[{"name":"Surgical Clinic Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"},{"name":"Department of Life Sciences, Cattinara University Hospital, Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8362-9044","authenticated-orcid":false,"given":"Nicol\u00f2","family":"de Manzini","sequence":"additional","affiliation":[{"name":"Surgical Clinic Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Palmisano","sequence":"additional","affiliation":[{"name":"Surgical Clinic Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3532-3200","authenticated-orcid":false,"given":"Mario","family":"Grassi","sequence":"additional","affiliation":[{"name":"Department of Engineering and Architecture, Trieste University, Via Valerio 6, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Parisi","sequence":"additional","affiliation":[{"name":"Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Pordenone,  33081 Aviano, Italy"},{"name":"Doctoral School in Molecular Biomedicine, University of Trieste, 34100 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3400-4363","authenticated-orcid":false,"given":"Flavio","family":"Rizzolio","sequence":"additional","affiliation":[{"name":"Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Pordenone,  33081 Aviano, Italy"},{"name":"Department of Molecular Sciences and Nanosystems, Ca\u2019 Foscari University of Venice, 30123 Venezia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0858-6192","authenticated-orcid":false,"given":"Domenico","family":"Tierno","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Cattinara University Hospital, Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Biasin","sequence":"additional","affiliation":[{"name":"Department of Engineering and Architecture, Trieste University, Via Valerio 6, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Grassi","sequence":"additional","affiliation":[{"name":"Degree Course in Medicine, University of Trieste, 34100 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhung Hai","family":"Truong","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Biotechnology, VNUHCM\u2014University of Science, Ho Chi Minh City 700000, Vietnam"},{"name":"Laboratory of Stem Cell Research and Application, VNUHCM\u2014University of Science, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9704-6651","authenticated-orcid":false,"given":"Gabriele","family":"Grassi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Cattinara University Hospital, Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. 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