{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:25:45Z","timestamp":1791188745969,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,3,5]],"date-time":"2003-03-05T00:00:00Z","timestamp":1046822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2003,6,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The constitutive activity of a number of growth and cell survival pathways are thought to contribute to the inherent resistance of melanoma to chemotherapy and radiotherapy. Many of these pathways are driven through the small GTPase Ras. Novel drugs such as the farnesyl transferase inhibitors (FTIs) and farnesyl thiosalicylic acid (FTS) interfere with the signaling of oncogenic Ras. The aim of our study was to assess the anti\u2010tumour activity of the FTI SCH66336 in melanoma and to assess whether SCH66336 and FTS could modulate chemoresistance in melanoma cells. SCH66336 had marked anti\u2010proliferative activity in both human and mouse melanoma cell lines, but not in non\u2010transformed NIH 3T3 cells. The anti\u2010proliferative activity of SCH66336 was due to G1\u2010phase cell cycle arrest and retinoblastoma protein inactivation, followed by apoptosis. Cisplatin, when administered alone, induced little apoptosis. In combination with cisplatin, both FTS and SCH66336 markedly enhanced the level of cisplatin\u2010induced apoptosis, an effect that was associated with enhanced G2\/M cell cycle arrest. Pharmacological inhibitors of either ERK or PI\u20103 kinase\/Akt did not mimic the chemosensitising activity of either SCH66336 or FTS. In summary, our study demonstrates that SCH66336 has good <jats:italic>in vitro<\/jats:italic> anti\u2010tumour activity in both human and mouse melanoma cell lines, and suggests that Ras antagonists could be useful in overcoming chemoresistance to cisplatin in melanoma. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.11064","type":"journal-article","created":{"date-parts":[[2003,4,2]],"date-time":"2003-04-02T17:37:48Z","timestamp":1049305068000},"page":"165-175","source":"Crossref","is-referenced-by-count":83,"title":["Farnesyl transferase inhibitor SCH66336 is cytostatic, pro\u2010apoptotic and enhances chemosensitivity to cisplatin in melanoma cells"],"prefix":"10.1002","volume":"105","author":[{"given":"Keiran S.M.","family":"Smalley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim G.","family":"Eisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,3,31]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(01)02013-5"},{"key":"e_1_2_5_3_2","first-page":"617","article-title":"Drug\u2010resistance in human melanoma. 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