{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:48:21Z","timestamp":1782899301500,"version":"3.54.5"},"reference-count":96,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Nacional del C\u00e1ncer","award":["PICT2018-0900"],"award-info":[{"award-number":["PICT2018-0900"]}]},{"name":"Instituto Nacional del C\u00e1ncer","award":["PICT2019-0801"],"award-info":[{"award-number":["PICT2019-0801"]}]},{"name":"Instituto Nacional del C\u00e1ncer","award":["PEICID-202-106"],"award-info":[{"award-number":["PEICID-202-106"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","award":["PICT2018-0900"],"award-info":[{"award-number":["PICT2018-0900"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","award":["PICT2019-0801"],"award-info":[{"award-number":["PICT2019-0801"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","award":["PEICID-202-106"],"award-info":[{"award-number":["PEICID-202-106"]}]},{"name":"Agencia Santafesina de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","award":["PICT2018-0900"],"award-info":[{"award-number":["PICT2018-0900"]}]},{"name":"Agencia Santafesina de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","award":["PICT2019-0801"],"award-info":[{"award-number":["PICT2019-0801"]}]},{"name":"Agencia Santafesina de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","award":["PEICID-202-106"],"award-info":[{"award-number":["PEICID-202-106"]}]},{"name":"Fundaci\u00f3n Florencio Fiorini","award":["PICT2018-0900"],"award-info":[{"award-number":["PICT2018-0900"]}]},{"name":"Fundaci\u00f3n Florencio Fiorini","award":["PICT2019-0801"],"award-info":[{"award-number":["PICT2019-0801"]}]},{"name":"Fundaci\u00f3n Florencio Fiorini","award":["PEICID-202-106"],"award-info":[{"award-number":["PEICID-202-106"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide and is responsible for numerous deaths. 5-fluorouracil (5-FU) is an effective chemotherapy drug commonly used in the treatment of CRC, either as monotherapy or in combination with other drugs. However, half of CRC cases are resistant to 5-FU-based therapies. To contribute to the understanding of the mechanisms underlying CRC resistance or recurrence after 5-FU-based therapies, we performed a comprehensive study integrating in silico, in vitro, and in vivo approaches. We identified differentially expressed genes and enrichment of pathways associated with recurrence after 5-FU-based therapies. Using these bioinformatics data as a starting point, we selected a group of drugs that restored 5-FU sensitivity to 5-FU resistant cells. Interestingly, treatment with the novel Rac1 inhibitor, 1A-116, reversed morphological changes associated with 5-FU resistance.. Moreover, our in vivo studies have shown that 1A-116 affected tumor growth and the development of metastasis. All our data allowed us to postulate that targeting Rac1 represents a promising avenue for the development of new treatments for patients with CRC resistant to 5-FU-based therapies.<\/jats:p>","DOI":"10.3390\/cells13211776","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T05:07:22Z","timestamp":1730092042000},"page":"1776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Overcoming Therapy Resistance in Colorectal Cancer: Targeting the Rac1 Signaling Pathway as a Potential Therapeutic Approach"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1494-2886","authenticated-orcid":false,"given":"Luciano E.","family":"Anselmino","sequence":"first","affiliation":[{"name":"Instituto de Inmunolog\u00eda Cl\u00ednica y Experimental de Rosario (IDICER, CONICET-UNR), Facultad de Ciencias M\u00e9dicas (UNR), Rosario 2000, 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