{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:26:09Z","timestamp":1787574369664,"version":"build-2736575974"},"reference-count":89,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cancer remains a highly complex and heterogeneous disease, causing major morbidity and mortality worldwide despite advances in diagnosis and treatment. The hallmarks of cancer enlighten the biological mechanisms supporting tumourigenesis and malignant evolution, while helping to identify potential therapeutic targets. Medical cannabis has mostly been used in oncology for supportive care, but increasing preclinical evidence suggests interference with cancer-related signalling pathways. This narrative review summarizes the current evidence on cannabinoids, in particular the phytocannabinoids cannabidiol (CBD) and \u03949-tetrahydrocannabinol (THC), framing their prospective anticancer effects in the hallmarks of cancer. Preclinical studies imply that CBD exerts antiproliferative effects by modulating oncogenic signalling pathways, including EGFR, PI3K\/AKT, RAS\/RAF\/ERK, mTOR and Wnt\/\u03b2-catenin, while also influencing tumour suppressor pathways involving p53, p21 and p27, causing cell cycle arrest. CBD has additionally been shown to promote programmed cell death via mitochondrial dysfunction and autophagy, altering cancer metabolism as well. Furthermore, CBD has shown anti-invasive and antiangiogenic properties and also appears to modulate immune responses and interactions with the tumour microenvironment, including emerging links with the microbiome. Overall, cannabinoids exhibit biologically plausible antitumour activity across multiple cancer hallmarks and may present promising candidates for combination therapeutic strategies. Nonetheless, the current evidence remains predominantly preclinical, and robust translational studies and clinical trials are needed to clarify their pharmacokinetic and pharmacodynamic profiles, determine their clinical efficacy and safety while assessing their potential integration into multimodal cancer treatment.<\/jats:p>","DOI":"10.3390\/ijms27177549","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Medical Cannabis and the Hallmarks of Cancer: A Critical Narrative Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-4681","authenticated-orcid":false,"given":"Diana","family":"Russo","sequence":"first","affiliation":[{"name":"Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-050X","authenticated-orcid":false,"given":"Rute","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3680-7757","authenticated-orcid":false,"given":"Val\u00e9ria","family":"Tavares","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Department of Pathology and Laboratory Medicine, RISE-Associate Laboratory (Health Research Network), Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences (EMCB), Fernando Pessoa University, 4420-096 Gondomar, Portugal"},{"name":"Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Agrelo","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Department of Pathology and Laboratory Medicine, RISE-Associate Laboratory (Health Research Network), Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences (EMCB), Fernando Pessoa University, 4420-096 Gondomar, Portugal"},{"name":"Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal"},{"name":"Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"European Cancer Organisation (ECO), 1040 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.3332\/ecancer.2026.2071","article-title":"The global cancer crisis: A review of growing burden, deepening inequality and initiatives for prevention and early detection","volume":"20","author":"Balch","year":"2026","journal-title":"ecancermedicalscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1016\/j.cell.2025.12.049","article-title":"Hallmarks of cancer-Then and now, and beyond","volume":"189","author":"Hanahan","year":"2026","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"157737","DOI":"10.1016\/j.phymed.2025.157737","article-title":"Unlocking the potential: Cannabidiol (CBD) as a promising anti-tumor agent","volume":"150","author":"Duan","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Peeri, H., and Koltai, H. 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