{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:29:53Z","timestamp":1786364993438,"version":"build-2736575974"},"reference-count":166,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia","award":["BNW-1-039\/N\/4\/F"],"award-info":[{"award-number":["BNW-1-039\/N\/4\/F"]}]},{"name":"Medical University of Silesia","award":["BNW-1-055\/N\/5\/F"],"award-info":[{"award-number":["BNW-1-055\/N\/5\/F"]}]},{"award":["BNW-1-039\/N\/4\/F"],"award-info":[{"award-number":["BNW-1-039\/N\/4\/F"]}],"id":[{"id":"https:\/\/ror.org\/005k7hp45","id-type":"ROR","asserted-by":"publisher"}]},{"award":["BNW-1-055\/N\/5\/F"],"award-info":[{"award-number":["BNW-1-055\/N\/5\/F"]}],"id":[{"id":"https:\/\/ror.org\/005k7hp45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide despite substantial advances in surgery, chemotherapy, targeted therapies, and immunotherapy. The limited efficacy of current treatment strategies in advanced disease and the emergence of therapeutic resistance highlight the urgent need for novel adjunctive therapeutic approaches. Increasing evidence indicates that chronic stress and sustained activation of \u03b2-adrenergic signaling promote colorectal tumor initiation, progression, angiogenesis, metastatic dissemination, and immune evasion, thereby identifying this pathway as a potential therapeutic target. Drug repurposing has emerged as an attractive strategy for accelerating the development of new anticancer therapies by identifying novel applications for clinically approved drugs with well-established safety profiles. Among these, \u03b2-blockers have gained considerable attention because of their ability to inhibit \u03b2-adrenergic signaling and modulate multiple oncogenic pathways implicated in CRC progression. Although accumulating preclinical and observational clinical evidence suggests that \u03b2-blockers may possess anticancer potential, the underlying molecular mechanisms and their translational relevance have not yet been comprehensively integrated. This review provides a critical overview of the current evidence regarding the therapeutic potential of \u03b2-blockers in CRC by integrating findings from preclinical and clinical studies. Particular emphasis is placed on the regulation of key signaling pathways, including cAMP\/PKA\/CREB, PI3K\/AKT\/mTOR, and RAS\/RAF\/MEK\/ERK, as well as on the effects of \u03b2-blockers on tumor cell proliferation, apoptosis, angiogenesis, epithelial\u2013mesenchymal transition, metastasis, and modulation of the tumor microenvironment and antitumor immune responses. However, significant barriers limit the translation of these findings into routine clinical practice, including the limited representativeness of preclinical models, potential hemodynamic adverse effects, and the inherent limitations of observational studies. Importantly, owing to the lack of prospective randomized clinical trials, the current evidence remains insufficient to establish the clinical efficacy of \u03b2-blockers in CRC. Although \u03b2-blockers possess several characteristics that make them attractive candidates for drug repurposing, including a well-established safety profile, widespread availability, and low cost, further mechanistic studies, prospective randomized clinical trials, and biomarker-based patient stratification are essential to determine their clinical efficacy and define their role in personalized CRC therapy.<\/jats:p>","DOI":"10.3390\/cancers18152507","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:16:22Z","timestamp":1785921382000},"page":"2507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting \u03b2-Adrenergic Signaling in Colorectal Cancer: Molecular Mechanisms and Therapeutic Potential of \u03b2-Blockers"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4938-7949","authenticated-orcid":false,"given":"Zuzanna","family":"Rogacz","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0236-8947","authenticated-orcid":false,"given":"Wiktoria Weronika","family":"Pacu\u0142a","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktor","family":"Janas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9812-4218","authenticated-orcid":false,"given":"Magda","family":"Markiewka","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Wala","sequence":"additional","affiliation":[{"name":"Silesia LabMed: Centre for Research and Implementation, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9815-3149","authenticated-orcid":false,"given":"Marcel","family":"Madej","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Silesia LabMed: Centre for Research and Implementation, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-2569","authenticated-orcid":false,"given":"Barbara","family":"Strza\u0142ka-Mrozik","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s43556-026-00433-4","article-title":"Colorectal Cancer Pathogenesis, Oncogenic Signaling Networks and Targeted Therapeutic Advances","volume":"7","author":"Chen","year":"2026","journal-title":"Mol. 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