{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T02:00:10Z","timestamp":1779933610982,"version":"3.53.1"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Oncol"],"DOI":"10.1007\/s12032-025-02790-6","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T20:03:19Z","timestamp":1748980999000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting Gastrointestinal Cancers with Cannabidiol: Mechanisms, Challenges, and Therapeutic Implications"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-7699","authenticated-orcid":false,"given":"Mojtaba","family":"Esmaeli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8298-4975","authenticated-orcid":false,"given":"Maryam","family":"Dehghanpour Dehabadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"issue":"3","key":"2790_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"CA: A Cancer J Clin"},{"issue":"10251","key":"2790_CR2","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0140-6736(20)31288-5","volume":"396","author":"EC Smyth","year":"2020","unstructured":"Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. The Lancet. 2020;396(10251):635\u201348.","journal-title":"The Lancet"},{"issue":"4","key":"2790_CR3","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","volume":"66","author":"M Arnold","year":"2017","unstructured":"Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683\u201391.","journal-title":"Gut"},{"issue":"10","key":"2790_CR4","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc3599","volume":"13","author":"C Holohan","year":"2013","unstructured":"Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13(10):714\u201326.","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"2790_CR5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrc706","volume":"2","author":"MM Gottesman","year":"2002","unstructured":"Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP\u2013dependent transporters. Nat Rev Cancer. 2002;2(1):48\u201358.","journal-title":"Nat Rev Cancer"},{"issue":"2","key":"2790_CR6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ctrv.2003.07.007","volume":"30","author":"J\u00c1F Vara","year":"2004","unstructured":"Vara J\u00c1F, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonz\u00e1lez-Bar\u00f3n M. PI3K\/Akt signalling pathway and cancer. Cancer Treat Rev. 2004;30(2):193\u2013204.","journal-title":"Cancer Treat Rev"},{"issue":"7","key":"2790_CR7","first-page":"3313","volume":"111","author":"G Ghiaur","year":"2008","unstructured":"Ghiaur G, Ferkowicz MJ, Milsom MD, Bailey J, Witte D, Cancelas JA, et al. Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells. Blood J Am Soc Hematol. 2008;111(7):3313\u201321.","journal-title":"Blood J Am Soc Hematol"},{"issue":"7467","key":"2790_CR8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature12626","volume":"501","author":"MR Junttila","year":"2013","unstructured":"Junttila MR, De Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501(7467):346\u201354.","journal-title":"Nature"},{"issue":"1","key":"2790_CR9","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1146\/annurev-pathol-011110-130235","volume":"6","author":"ER Fearon","year":"2011","unstructured":"Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011;6(1):479\u2013507.","journal-title":"Annu Rev Pathol"},{"issue":"4","key":"2790_CR10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nrc1318","volume":"4","author":"ST Sonis","year":"2004","unstructured":"Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4(4):277\u201384.","journal-title":"Nat Rev Cancer"},{"issue":"Suppl. 2","key":"2790_CR11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000443404","volume":"25","author":"GM Cragg","year":"2016","unstructured":"Cragg GM, Pezzuto JM. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract. 2016;25(Suppl. 2):41\u201359.","journal-title":"Med Princ Pract"},{"issue":"9","key":"2790_CR12","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1080\/15384101.2020.1742952","volume":"19","author":"O Kovalchuk","year":"2020","unstructured":"Kovalchuk O, Kovalchuk I. Cannabinoids as anticancer therapeutic agents. Cell Cycle. 2020;19(9):961\u201389.","journal-title":"Cell Cycle"},{"issue":"16","key":"2790_CR13","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1007\/s40265-018-0996-1","volume":"78","author":"AI Fraguas-S\u00e1nchez","year":"2018","unstructured":"Fraguas-S\u00e1nchez AI, Torres-Su\u00e1rez AI. Medical use of cannabinoids. Drugs. 2018;78(16):1665\u2013703.","journal-title":"Drugs"},{"issue":"2","key":"2790_CR14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1365-2125.2012.04298.x","volume":"75","author":"P Massi","year":"2013","unstructured":"Massi P, Solinas M, Cinquina V, Parolaro D. Cannabidiol as potential anticancer drug. Br J Clin Pharmacol. 2013;75(2):303\u201312.","journal-title":"Br J Clin Pharmacol"},{"issue":"10","key":"2790_CR15","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1002\/ijc.22917","volume":"121","author":"A Greenhough","year":"2007","unstructured":"Greenhough A, Patsos HA, Williams AC, Paraskeva C. The cannabinoid \u03b49-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Int J Cancer. 2007;121(10):2172\u201380.","journal-title":"Int J Cancer"},{"issue":"11","key":"2790_CR16","first-page":"3799","volume":"31","author":"S Sreevalsan","year":"2011","unstructured":"Sreevalsan S, Joseph S, Jutooru I, Chadalapaka G, Safe SH. Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent. Anticancer Res. 2011;31(11):3799\u2013807.","journal-title":"Anticancer Res"},{"key":"2790_CR17","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s00109-012-0957-1","volume":"91","author":"J Kargl","year":"2013","unstructured":"Kargl J, Haybaeck J, Stan\u010di\u0107 A, Andersen L, Marsche G, Heinemann A, et al. O-1602, an atypical cannabinoid, inhibits tumor growth in colitis-associated colon cancer through multiple mechanisms. J Mol Med. 2013;91:449\u201358.","journal-title":"J Mol Med"},{"issue":"5","key":"2790_CR18","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.phymed.2013.11.006","volume":"21","author":"B Romano","year":"2014","unstructured":"Romano B, Borrelli F, Pagano E, Cascio MG, Pertwee RG, Izzo AA. Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Phytomedicine. 2014;21(5):631\u20139.","journal-title":"Phytomedicine"},{"issue":"42","key":"2790_CR19","doi-asserted-by":"crossref","first-page":"68781","DOI":"10.18632\/oncotarget.11968","volume":"7","author":"E Mart\u00ednez-Mart\u00ednez","year":"2016","unstructured":"Mart\u00ednez-Mart\u00ednez E, Mart\u00edn-Ruiz A, Mart\u00edn P, Calvo V, Provencio M, Garc\u00eda JM. CB2 cannabinoid receptor activation promotes colon cancer progression via AKT\/GSK3\u03b2 signaling pathway. Oncotarget. 2016;7(42):68781.","journal-title":"Oncotarget"},{"issue":"1","key":"2790_CR20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/ijc.31030","volume":"142","author":"C Hasenoehrl","year":"2018","unstructured":"Hasenoehrl C, Feuersinger D, Sturm EM, B\u00e4rnthaler T, Heitzer E, Graf R, et al. G protein-coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1. Int J Cancer. 2018;142(1):121\u201332.","journal-title":"Int J Cancer"},{"key":"2790_CR21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00580-018-2810-6","volume":"28","author":"M Honarmand","year":"2019","unstructured":"Honarmand M, Namazi F, Mohammadi A, Nazifi S. Can cannabidiol inhibit angiogenesis in colon cancer? Comp Clin Pathol. 2019;28:165\u201372.","journal-title":"Comp Clin Pathol"},{"issue":"6","key":"2790_CR22","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3390\/cancers11060781","volume":"11","author":"S Jeong","year":"2019","unstructured":"Jeong S, Kim BG, Kim DY, Kim BR, Kim JL, Park SH, et al. Cannabidiol overcomes oxaliplatin resistance by enhancing NOS3-and SOD2-induced autophagy in human colorectal cancer cells. Cancers. 2019;11(6):781.","journal-title":"Cancers"},{"issue":"5","key":"2790_CR23","doi-asserted-by":"crossref","first-page":"642","DOI":"10.3390\/cancers11050642","volume":"11","author":"JL Kim","year":"2019","unstructured":"Kim JL, Kim BR, Kim DY, Jeong YA, Jeong S, Na YJ, et al. Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer. Cancers. 2019;11(5):642.","journal-title":"Cancers"},{"issue":"8","key":"2790_CR24","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3390\/biom9080302","volume":"9","author":"X Zhang","year":"2019","unstructured":"Zhang X, Qin Y, Pan Z, Li M, Liu X, Chen X, et al. Cannabidiol induces cell cycle arrest and cell apoptosis in human gastric cancer SGC-7901 cells. Biomolecules. 2019;9(8):302.","journal-title":"Biomolecules"},{"issue":"11","key":"2790_CR25","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/s41419-019-2001-7","volume":"10","author":"S Jeong","year":"2019","unstructured":"Jeong S, Jo MJ, Yun HK, Kim DY, Kim BR, Kim JL, et al. Cannabidiol promotes apoptosis via regulation of XIAP\/Smac in gastric cancer. Cell Death Dis. 2019;10(11):846.","journal-title":"Cell Death Dis"},{"issue":"1","key":"2790_CR26","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1186\/s13104-020-05229-5","volume":"13","author":"A Sainz-Cort","year":"2020","unstructured":"Sainz-Cort A, M\u00fcller-S\u00e1nchez C, Espel E. Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum. BMC Res Notes. 2020;13(1):389.","journal-title":"BMC Res Notes"},{"issue":"15","key":"2790_CR27","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.3390\/ijms21155533","volume":"21","author":"D Cerretani","year":"2020","unstructured":"Cerretani D, Collodel G, Brizzi A, Fiaschi AI, Menchiari A, Moretti E, et al. Cytotoxic effects of cannabinoids on human HT-29 colorectal adenocarcinoma cells: different mechanisms of THC, CBD, and CB83. Int J Mol Sci. 2020;21(15):5533.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"2790_CR28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2174\/1871520620666200415102321","volume":"21","author":"NW Nkune","year":"2021","unstructured":"Nkune NW, Kruger CA, Abrahamse H. Possible enhancement of photodynamic therapy (PDT) colorectal cancer treatment when combined with cannabidiol. Anti-Cancer Agents Med Chem (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2021;21(2):137\u201348.","journal-title":"Anti-Cancer Agents Med Chem (Formerly Current Medicinal Chemistry-Anti-Cancer Agents)"},{"issue":"19","key":"2790_CR29","doi-asserted-by":"crossref","first-page":"11366","DOI":"10.3390\/ijms231911366","volume":"23","author":"D Ben-Ami Shor","year":"2022","unstructured":"Ben-Ami Shor D, Hochman I, Gluck N, Shibolet O, Scapa E. The cytotoxic effect of isolated cannabinoid extracts on polypoid colorectal tissue. Int J Mol Sci. 2022;23(19):11366.","journal-title":"Int J Mol Sci"},{"key":"2790_CR30","doi-asserted-by":"crossref","first-page":"156","DOI":"10.18632\/oncotarget.28171","volume":"13","author":"NW Nkune","year":"2022","unstructured":"Nkune NW, Kruger CA, Abrahamse H. Synthesis of a novel nanobioconjugate for targeted photodynamic therapy of colon cancer enhanced with cannabidiol. Oncotarget. 2022;13:156.","journal-title":"Oncotarget"},{"issue":"10","key":"2790_CR31","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.3390\/ph15101166","volume":"15","author":"A Benedicto","year":"2022","unstructured":"Benedicto A, Arteta B, Duranti A, Alonso-Alconada D. The synthetic cannabinoid URB447 exerts antitumor and antimetastatic effect in melanoma and colon cancer. Pharmaceuticals. 2022;15(10):1166.","journal-title":"Pharmaceuticals"},{"key":"2790_CR32","doi-asserted-by":"crossref","first-page":"1145666","DOI":"10.3389\/fphar.2023.1145666","volume":"14","author":"B Y\u00fcksel","year":"2023","unstructured":"Y\u00fcksel B, H\u0131zl\u0131 Deniz AA, \u015eahin F, Sahin K, T\u00fcrkel N. Cannabinoid compounds in combination with curcumin and piperine display an anti-tumorigenic effect against colon cancer cells. Front Pharmacol. 2023;14:1145666.","journal-title":"Front Pharmacol"},{"issue":"1","key":"2790_CR33","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/s41420-023-01578-9","volume":"9","author":"F Wang","year":"2023","unstructured":"Wang F, Dezfouli AB, Khosravi M, Sievert W, Stangl S, Schwab M, et al. Cannabidiol-induced crosstalk of apoptosis and macroautophagy in colorectal cancer cells involves p53 and Hsp70. Cell Death Discovery. 2023;9(1):286.","journal-title":"Cell Death Discovery"},{"issue":"19","key":"2790_CR34","doi-asserted-by":"crossref","first-page":"14743","DOI":"10.3390\/ijms241914743","volume":"24","author":"V Cherkasova","year":"2023","unstructured":"Cherkasova V, Ilnytskyy Y, Kovalchuk O, Kovalchuk I. Transcriptome analysis of cisplatin, cannabidiol, and intermittent serum starvation alone and in various combinations on colorectal cancer cells. Int J Mol Sci. 2023;24(19):14743.","journal-title":"Int J Mol Sci"},{"issue":"23","key":"2790_CR35","doi-asserted-by":"crossref","first-page":"16621","DOI":"10.3390\/ijms242316621","volume":"24","author":"I-S Kwon","year":"2023","unstructured":"Kwon I-S, Hwang Y-N, Park J-H, Na H-H, Kwon T-H, Park J-S, et al. Metallothionein family proteins as regulators of zinc ions synergistically enhance the anticancer effect of cannabidiol in human colorectal cancer cells. Int J Mol Sci. 2023;24(23):16621.","journal-title":"Int J Mol Sci"},{"issue":"7","key":"2790_CR36","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.jpha.2023.04.013","volume":"13","author":"X Sun","year":"2023","unstructured":"Sun X, Zhou L, Wang Y, Deng G, Cao X, Ke B, et al. Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer. J Pharm Anal. 2023;13(7):726\u201344.","journal-title":"J Pharm Anal"},{"issue":"4","key":"2790_CR37","doi-asserted-by":"crossref","first-page":"3626","DOI":"10.3390\/cimb46040227","volume":"46","author":"D B\u0119ben","year":"2024","unstructured":"B\u0119ben D, Siwiela O, Szyjka A, Graczyk M, Rzepka D, Barg E, et al. Phytocannabinoids CBD, CBG, and their derivatives CBD-HQ and CBG-A induced in vitro cytotoxicity in 2D and 3D colon cancer cell models. Curr Issues Mol Biol. 2024;46(4):3626\u201339.","journal-title":"Curr Issues Mol Biol"},{"issue":"11","key":"2790_CR38","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.3390\/ph17111465","volume":"17","author":"F Li","year":"2024","unstructured":"Li F, Gong H, Jia X, Gao C, Jia P, Zhao X, et al. RNAi screen identifies AXL inhibition combined with cannabinoid WIN55212-2 as a potential strategy for cancer treatment. Pharmaceuticals. 2024;17(11):1465.","journal-title":"Pharmaceuticals"},{"issue":"23","key":"2790_CR39","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.3390\/polym16233273","volume":"16","author":"DK Baines","year":"2024","unstructured":"Baines DK, Wright K, Douglas TE. Preliminary in vitro assessment of whey protein isolate hydrogel with Cannabidiol as a potential hydrophobic oral drug delivery system for colorectal cancer therapy. Polymers. 2024;16(23):3273.","journal-title":"Polymers"},{"key":"2790_CR40","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/bs.acr.2022.02.007","volume":"155","author":"HI Akbarali","year":"2022","unstructured":"Akbarali HI, Muchhala KH, Jessup DK, Cheatham S. Chemotherapy induced gastrointestinal toxicities. Adv Cancer Res. 2022;155:131\u201366.","journal-title":"Adv Cancer Res"},{"key":"2790_CR41","first-page":"353","volume-title":"Toxic effects of cancer therapies Public Health and Toxicology Issues Drug Research","author":"S Ingole","year":"2024","unstructured":"Ingole S, Vasdev N, Tekade M, Gupta T, Pawar B, Mhatre M, et al. Toxic effects of cancer therapies Public Health and Toxicology Issues Drug Research. Amsertdam: Elsevier; 2024. p. 353\u201379."},{"issue":"7","key":"2790_CR42","doi-asserted-by":"crossref","first-page":"713","DOI":"10.2174\/1389450120666191127113854","volume":"21","author":"LV Spirina","year":"2020","unstructured":"Spirina LV, Avgustinovich AV, Afanas\u2019 ev SG, Cheremisina OV, Volkov MY, Choynzonov EL, et al. Molecular mechanism of resistance to chemotherapy in gastric cancers, the role of autophagy. Curr Drug Targets. 2020;21(7):713\u201321.","journal-title":"Curr Drug Targets"},{"key":"2790_CR43","first-page":"1230591","volume":"14","author":"T Shi","year":"2023","unstructured":"Shi T, Wang H, Wei J, Wang J, Fan Y, Zheng C, et al. Gastrointestinal cancer immunotherapy: from drug resistance mechanisms to overcoming strategies. Front Media SA. 2023;14:1230591.","journal-title":"Front Media SA"},{"key":"2790_CR44","first-page":"7983","volume":"312","author":"M Sodergren","year":"2024","unstructured":"Sodergren M, Mangal N. Cannabidiol as a chemotherapy adjunct in cancer treatment. Pharm J. 2024;312:7983.","journal-title":"Pharm J"},{"issue":"5","key":"2790_CR45","doi-asserted-by":"crossref","first-page":"766","DOI":"10.3390\/biom11050766","volume":"11","author":"C Griffiths","year":"2021","unstructured":"Griffiths C, Aikins J, Warshal D, Ostrovsky O. Can cannabidiol affect the efficacy of chemotherapy and epigenetic treatments in cancer? Biomolecules. 2021;11(5):766.","journal-title":"Biomolecules"},{"key":"2790_CR46","doi-asserted-by":"crossref","first-page":"1094020","DOI":"10.3389\/fphar.2023.1094020","volume":"14","author":"Z Fu","year":"2023","unstructured":"Fu Z, Zhao P-Y, Yang X-P, Li H, Hu S-D, Xu Y-X, et al. Cannabidiol regulates apoptosis and autophagy in inflammation and cancer: A review. Front Pharmacol. 2023;14:1094020.","journal-title":"Front Pharmacol"},{"issue":"1","key":"2790_CR47","doi-asserted-by":"crossref","first-page":"4619760","DOI":"10.1155\/2022\/4619760","volume":"2022","author":"L Li","year":"2022","unstructured":"Li L, Xuan Y, Zhu B, Wang X, Tian X, Zhao L, et al. Protective effects of Cannabidiol on chemotherapy-induced oral mucositis via the Nrf2\/Keap1\/ARE signaling pathways. Oxid Med Cell Longev. 2022;2022(1):4619760.","journal-title":"Oxid Med Cell Longev"},{"issue":"7","key":"2790_CR48","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1007\/s00432-022-04265-x","volume":"149","author":"P Feng","year":"2023","unstructured":"Feng P, Zhu L, Jie J, Yang P, Sheng N, Chen X, et al. Cannabidiol inhibits invasion and metastasis in colorectal cancer cells by reversing epithelial\u2013mesenchymal transition through the Wnt\/\u03b2-catenin signaling pathway. J Cancer Res Clin Oncol. 2023;149(7):3587\u201398.","journal-title":"J Cancer Res Clin Oncol"},{"issue":"10","key":"2790_CR49","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1080\/17474124.2017.1367663","volume":"11","author":"E Pagano","year":"2017","unstructured":"Pagano E, Borrelli F. Targeting cannabinoid receptors in gastrointestinal cancers for therapeutic uses: current status and future perspectives. Expert Rev Gastroenterol Hepatol. 2017;11(10):871\u20133.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"issue":"9","key":"2790_CR50","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.3390\/molecules29091943","volume":"29","author":"L Ma","year":"2024","unstructured":"Ma L, Liu M, Liu C, Zhang H, Yang S, An J, et al. Research progress on the mechanism of the antitumor effects of Cannabidiol. Molecules. 2024;29(9):1943.","journal-title":"Molecules"},{"issue":"6","key":"2790_CR51","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.3390\/ijms23063344","volume":"23","author":"C Pagano","year":"2022","unstructured":"Pagano C, Navarra G, Coppola L, Avilia G, Bifulco M, Laezza C. Cannabinoids: therapeutic use in clinical practice. Int J Mol Sci. 2022;23(6):3344.","journal-title":"Int J Mol Sci"},{"key":"2790_CR52","doi-asserted-by":"crossref","first-page":"4493","DOI":"10.1007\/s00018-016-2303-1","volume":"73","author":"L Sun","year":"2016","unstructured":"Sun L, Fang J. Epigenetic regulation of epithelial\u2013mesenchymal transition. Cell Mol Life Sci. 2016;73:4493\u2013515.","journal-title":"Cell Mol Life Sci"},{"key":"2790_CR53","doi-asserted-by":"crossref","first-page":"960539","DOI":"10.3389\/fonc.2022.960539","volume":"12","author":"Y Yang","year":"2022","unstructured":"Yang Y, Meng W-J, Wang Z-Q. The origin of gastric cancer stem cells and their effects on gastric cancer: Novel therapeutic targets for gastric cancer. Front Oncol. 2022;12:960539.","journal-title":"Front Oncol"},{"issue":"5","key":"2790_CR54","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","volume":"139","author":"JP Thiery","year":"2009","unstructured":"Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871\u201390.","journal-title":"Cell"},{"issue":"6","key":"2790_CR55","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3390\/biology11060817","volume":"11","author":"CG Heider","year":"2022","unstructured":"Heider CG, Itenberg SA, Rao J, Ma H, Wu X. Mechanisms of cannabidiol (CBD) in cancer treatment: a review. Biology. 2022;11(6):817.","journal-title":"Biology"},{"issue":"3","key":"2790_CR56","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/ejp.1118","volume":"22","author":"W H\u00e4user","year":"2018","unstructured":"H\u00e4user W, Petzke F, Fitzcharles M. Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management\u2013An overview of systematic reviews. Eur J Pain. 2018;22(3):455\u201370.","journal-title":"Eur J Pain"},{"key":"2790_CR57","doi-asserted-by":"crossref","unstructured":"Moniruzzaman M, Wong KY, Janjua TI, Martin JH, Begun J, Popat A. Cannabidiol Targets Colorectal Cancer Cells via Cannabinoid Receptor 2, Independent of Common Mutations. ACS Pharmacology & Translational Science. 2025.","DOI":"10.1021\/acsptsci.4c00644"},{"issue":"6","key":"2790_CR58","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2174\/1566524016666160523143937","volume":"16","author":"W Rozpedek","year":"2016","unstructured":"Rozpedek W, Pytel D, Mucha B, Leszczynska H, Diehl JA, Majsterek I. The role of the PERK\/eIF2\u03b1\/ATF4\/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress. Curr Mol Med. 2016;16(6):533\u201344.","journal-title":"Curr Mol Med"},{"issue":"1","key":"2790_CR59","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3390\/cells9010219","volume":"9","author":"N Garcia-Carbonero","year":"2020","unstructured":"Garcia-Carbonero N, Martinez-Useros J, Li W, Orta A, Perez N, Carames C, et al. KRAS and BRAF mutations as prognostic and predictive biomarkers for standard chemotherapy response in metastatic colorectal cancer: a single institutional study. Cells. 2020;9(1):219.","journal-title":"Cells"},{"issue":"1","key":"2790_CR60","doi-asserted-by":"crossref","first-page":"22230","DOI":"10.1038\/s41598-023-48768-0","volume":"13","author":"J-T Huo","year":"2023","unstructured":"Huo J-T, Tuersun A, Yu S-Y, Zhang Y-C, Feng W-Q, Xu Z-Q, et al. Leveraging a KRAS-based signature to predict the prognosis and drug sensitivity of colon cancer and identifying SPINK4 as a new biomarker. Sci Rep. 2023;13(1):22230.","journal-title":"Sci Rep"},{"key":"2790_CR61","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.canlet.2019.01.011","volume":"447","author":"S Jeong","year":"2019","unstructured":"Jeong S, Yun HK, Jeong YA, Jo MJ, Kang SH, Kim JL, et al. Cannabidiol-induced apoptosis is mediated by activation of Noxa in human colorectal cancer cells. Cancer Lett. 2019;447:12\u201323.","journal-title":"Cancer Lett"},{"issue":"11","key":"2790_CR62","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.3390\/cancers12113203","volume":"12","author":"ES Seltzer","year":"2020","unstructured":"Seltzer ES, Watters AK, MacKenzie D, Granat LM, Zhang D. Cannabidiol (CBD) as a promising anti-cancer drug. Cancers. 2020;12(11):3203.","journal-title":"Cancers"},{"key":"2790_CR63","doi-asserted-by":"crossref","first-page":"425858","DOI":"10.3389\/fphar.2018.01365","volume":"9","author":"SA Millar","year":"2018","unstructured":"Millar SA, Stone NL, Yates AS, O\u2019Sullivan SE. A systematic review on the pharmacokinetics of cannabidiol in humans. Front Pharmacol. 2018;9:425858.","journal-title":"Front Pharmacol"},{"issue":"8","key":"2790_CR64","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s40263-020-00741-5","volume":"34","author":"E Perucca","year":"2020","unstructured":"Perucca E, Bialer M. Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. CNS Drugs. 2020;34(8):795\u2013800.","journal-title":"CNS Drugs"},{"issue":"4","key":"2790_CR65","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3390\/ph16040487","volume":"16","author":"E Assadpour","year":"2023","unstructured":"Assadpour E, Rezaei A, Das SS, Krishna Rao BV, Singh SK, Kharazmi MS, et al. Cannabidiol-loaded nanocarriers and their therapeutic applications. Pharmaceuticals. 2023;16(4):487.","journal-title":"Pharmaceuticals"},{"key":"2790_CR66","doi-asserted-by":"crossref","first-page":"1063775","DOI":"10.3389\/fphar.2023.1063775","volume":"14","author":"Y Yu","year":"2023","unstructured":"Yu Y, Yu R, Wang N, Bai Y, Shi Q, Maswikiti EP, et al. Photodynamic therapy in combination with immune checkpoint inhibitors plus chemotherapy for first-line treatment in advanced or metastatic gastric or gastroesophageal junction cancer: A phase 2\u20133 clinical trial protocol. Front Pharmacol. 2023;14:1063775.","journal-title":"Front Pharmacol"},{"issue":"10","key":"2790_CR67","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/j.humpath.2011.12.014","volume":"43","author":"J Arriaga","year":"2012","unstructured":"Arriaga J, Bravo I, Bruno L, Bayo SM, Hannois A, Loria FS, et al. Combined metallothioneins and p53 proteins expression as a prognostic marker in patients with Dukes stage B and C colorectal cancer. Hum Pathol. 2012;43(10):1695\u2013703.","journal-title":"Hum Pathol"},{"issue":"11","key":"2790_CR68","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.annonc.2020.07.020","volume":"31","author":"P Grimison","year":"2020","unstructured":"Grimison P, Mersiades A, Kirby A, Lintzeris N, Morton R, Haber P, et al. Oral THC: CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial. Ann Oncol. 2020;31(11):1553\u201360.","journal-title":"Ann Oncol"},{"key":"2790_CR69","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD009464.pub2","author":"LA Smith","year":"2015","unstructured":"Smith LA, Azariah F, Lavender VT, Stoner NS, Bettiol S. Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database of Syst Rev. 2015. https:\/\/doi.org\/10.1002\/14651858.CD009464.pub2.","journal-title":"Cochrane Database of Syst Rev"},{"issue":"7303","key":"2790_CR70","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1136\/bmj.323.7303.16","volume":"323","author":"MR Tram\u00e8r","year":"2001","unstructured":"Tram\u00e8r MR, Carroll D, Campbell FA, Reynolds DJM, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 2001;323(7303):16.","journal-title":"BMJ"},{"key":"2790_CR71","first-page":"221","volume":"7","author":"EM Rock","year":"2016","unstructured":"Rock EM, Parker LA. Cannabinoids as potential treatment for chemotherapy-induced nausea and vomiting. Front Pharmacol. 2016;7:221.","journal-title":"Front Pharmacol"},{"issue":"34","key":"2790_CR72","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1200\/JCO.23.01836","volume":"42","author":"P Grimison","year":"2024","unstructured":"Grimison P, Mersiades A, Kirby A, Tognela A, Olver I, Morton RL, et al. Oral cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: final results of a randomized, placebo-controlled, phase II\/III trial. J Clin Oncol. 2024;42(34):4040\u201350.","journal-title":"J Clin Oncol"},{"issue":"3","key":"2790_CR73","first-page":"320","volume":"6","author":"SS S\u00e1","year":"2023","unstructured":"S\u00e1 SS, Melo-Alvim C, Reis-Pina P. Effects of cannabinoids on pain control, quality of life and opioid-sparing in cancer patients: systematic review. BrJP. 2023;6(3):320\u20139.","journal-title":"BrJP"},{"issue":"7","key":"2790_CR74","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1200\/JCO.22.01632","volume":"41","author":"J Hardy","year":"2023","unstructured":"Hardy J, Greer R, Huggett G, Kearney A, Gurgenci T, Good P. Phase IIb randomized, placebo-controlled, dose-escalating, double-blind study of cannabidiol oil for the relief of symptoms in advanced cancer (MedCan1-CBD). J Clin Oncol. 2023;41(7):1444\u201352.","journal-title":"J Clin Oncol"},{"key":"2790_CR75","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.2147\/IJWH.S401938","volume":"15","author":"A Sukpiriyagul","year":"2023","unstructured":"Sukpiriyagul A, Chartchaiyarerk R, Tabtipwon P, Smanchat B, Prommas S, Bhamarapravatana K, et al. Oral tetrahydrocannabinol (THC): cannabinoid (CBD) cannabis extract adjuvant for reducing chemotherapy-induced nausea and vomiting (CINV): a randomized, double-blinded, placebo-controlled, crossover trial. Int J Women\u2019s Health. 2023;15:1345\u201352.","journal-title":"Int J Women\u2019s Health"},{"issue":"8","key":"2790_CR76","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.3390\/pharmaceutics15082120","volume":"15","author":"L Brstilo","year":"2023","unstructured":"Brstilo L, Reyes Valenzuela G, Caraballo R, P\u00e9rez Montilla C, Garc\u00eda Bournissen F, C\u00e1ceres Guido P, et al. Real-world evidence of factors affecting cannabidiol exposure in children with drug-resistant developmental and epileptic encephalopathies. Pharmaceutics. 2023;15(8):2120.","journal-title":"Pharmaceutics"},{"key":"2790_CR77","doi-asserted-by":"crossref","first-page":"713153","DOI":"10.3389\/fmed.2021.713153","volume":"8","author":"M Zaiachuk","year":"2021","unstructured":"Zaiachuk M, Pryimak N, Kovalchuk O, Kovalchuk I. Cannabinoids, medical cannabis, and colorectal cancer immunotherapy. Front Med. 2021;8:713153.","journal-title":"Front Med"},{"issue":"2","key":"2790_CR78","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.soc.2017.11.008","volume":"27","author":"K Mody","year":"2018","unstructured":"Mody K, Bekaii-Saab T. Clinical trials and progress in metastatic colon cancer. Surg Oncol Clin. 2018;27(2):349\u201365.","journal-title":"Surg Oncol Clin"},{"key":"2790_CR79","doi-asserted-by":"crossref","first-page":"1211506","DOI":"10.3389\/fphar.2023.1211506","volume":"14","author":"I Creanga-Murariu","year":"2023","unstructured":"Creanga-Murariu I, Filipiuc LE, Cuciureanu M, Tamba B-I, Alexa-Stratulat T. Should oncologists trust cannabinoids? Front Pharmacol. 2023;14:1211506.","journal-title":"Front Pharmacol"},{"issue":"3","key":"2790_CR80","doi-asserted-by":"crossref","first-page":"e089336","DOI":"10.1136\/bmjopen-2024-089336","volume":"15","author":"OM Bellas","year":"2025","unstructured":"Bellas OM, Cao K, Bowen J, Smid S, Shakib S, Crawford GB, et al. Medicinal CANnabis (CBD\/THC) to prevent the symptoms and side effects of chemotherapy in people with advanced CANcer (CANCAN): protocol for a phase II, randomised, double-blind, placebo-controlled trial. BMJ Open. 2025;15(3):e089336.","journal-title":"BMJ Open"},{"key":"2790_CR81","doi-asserted-by":"crossref","unstructured":"Wiley J, Gourdet C, Thomas B. Cannabidiol: Science, Marketing, and Legal Perspectives. 2020 [cited 2023 Jul 26].","DOI":"10.3768\/rtipress.2020.op.0065.2004"},{"issue":"1","key":"2790_CR82","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1089\/can.2019.0010","volume":"4","author":"D Piomelli","year":"2019","unstructured":"Piomelli D, Solomon R, Abrams D, Balla A, Grant I, Marcotte T, et al. Regulatory barriers to research on cannabis and cannabinoids: a proposed path forward. Cannabis and cannabinoid research. 2019;4(1):21\u201332.","journal-title":"Cannabis and cannabinoid research"},{"issue":"58","key":"2790_CR83","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1093\/jncimonographs\/lgab009","volume":"2021","author":"ZD Cooper","year":"2021","unstructured":"Cooper ZD, Abrams DI, Gust S, Salicrup A, Throckmorton DC. Challenges for clinical cannabis and cannabinoid research in the United States. JNCI Monographs. 2021;2021(58):114\u201322.","journal-title":"JNCI Monographs"},{"key":"2790_CR84","doi-asserted-by":"crossref","unstructured":"Hughes B, Vandam L, Mounteney J, Griffiths P. Regulatory approaches to cannabidiol in the European Union: are market developments sowing the seeds of confusion? : Wiley Online Library; 2022. p. 3\u20134.","DOI":"10.1111\/add.15587"},{"issue":"3","key":"2790_CR85","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S1734-1140(12)70871-X","volume":"64","author":"JC Arnold","year":"2012","unstructured":"Arnold JC, Hone P, Holland ML, Allen JD. CB2 and TRPV1 receptors mediate cannabinoid actions on MDR1 expression in multidrug resistant cells. Pharmacol Rep. 2012;64(3):751\u20137.","journal-title":"Pharmacol Rep"},{"key":"2790_CR86","first-page":"13","volume":"26","author":"M Dieng","year":"2024","unstructured":"Dieng M, Grimison PS, Kirby A, Mersiades A, Pokorski I, Stockler MR, et al. Cost-effectiveness of an oral THC: CBD cannabis extract for secondary prevention of refractory, chemotherapy-induced nausea and vomiting. Am Soc Clin Oncol. 2024;26:13.","journal-title":"Am Soc Clin Oncol"},{"issue":"3","key":"2790_CR87","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.joim.2023.03.004","volume":"21","author":"SM Tambe","year":"2023","unstructured":"Tambe SM, Mali S, Amin PD, Oliveira M. Neuroprotective potential of cannabidiol: Molecular mechanisms and clinical implications. J Integr Med. 2023;21(3):236\u201344.","journal-title":"J Integr Med"}],"container-title":["Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-02790-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12032-025-02790-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-02790-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T08:40:14Z","timestamp":1751532014000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12032-025-02790-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,3]]},"references-count":87,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["2790"],"URL":"https:\/\/doi.org\/10.1007\/s12032-025-02790-6","relation":{},"ISSN":["1559-131X"],"issn-type":[{"value":"1559-131X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,3]]},"assertion":[{"value":"25 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"The authors have carefully addressed ethical considerations, including monitoring for text plagiarism, duplicate publications, research misconduct, data fabrication, and falsification.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"237"}}