{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:38Z","timestamp":1785409838939,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"crossref","award":["22K12393"],"award-info":[{"award-number":["22K12393"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"award":["22K12393"],"award-info":[{"award-number":["22K12393"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Resistance to combined BRAF and MEK inhibition remains a major barrier to durable disease control in BRAF-mutant melanoma. Acyclic retinoid (ACR; peretinoin) is a clinically studied retinoid, but its activity in MAPK inhibitor-resistant melanoma remains incompletely defined. Here, we established A375P-derived dabrafenib plus trametinib-resistant clones and evaluated ACR mainly in the A375PDTR-D clone as an in vitro proof-of-concept model. Resistant clones retained higher viability and failed to suppress ERK phosphorylation under dabrafenib plus trametinib treatment. In A375PDTR-D cells, ACR reduced short-term viability and clonogenic growth and was associated with decreased STAT3 Tyr705 phosphorylation, reduced EGFR, Cyclin D1, and Cyclin B1 expression, and increased p27KIP1. ACR did not detectably suppress AKT, MEK\/ERK, or basal JNK phosphorylation under the tested conditions. These findings support further investigation of ACR as a candidate non-MAPK adjunct strategy; however, generalizability to broader melanoma models, formal drug-interaction status, direct cell-cycle\/apoptosis effects, clinically achievable exposure, and in vivo efficacy remain to be established.<\/jats:p>","DOI":"10.3390\/ijms27146245","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:04:31Z","timestamp":1784016271000},"page":"6245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acyclic Retinoid Attenuates STAT3 Signaling and Reduces In Vitro Growth of A375-Derived Dabrafenib Plus Trametinib-Resistant Melanoma Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Mitsuaki","family":"Nishizawa","sequence":"first","affiliation":[{"name":"Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama 337-8570, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama 337-8570, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinata","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama 337-8570, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8705-9870","authenticated-orcid":false,"given":"Ichiro","family":"Yajima","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama 337-8570, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","unstructured":"IARC (2026, July 03). 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