{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:21:17Z","timestamp":1781108477116,"version":"3.54.1"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,11,23]]},"abstract":"<jats:p>\n                    During past decades, knowledge of melanoma biology has increased considerably. Numerous therapeutic modalities based on this knowledge are currently under investigation. Advanced melanoma, nevertheless, remains a prime example of poor treatment response that may, in part, be the consequence of activated N-Ras oncoproteins. Besides oncogenic Ras, wild-type Ras gene products also play a key role in receptor tyrosine kinase growth factor signaling, known to be of importance in oncogenesis and tumor progression of a variety of human neoplasms, including malignant melanoma; therefore, it is reasonable to speculate that a pharmacological approach that curtails Ras activity may represent a sensible approach to inhibit melanoma growth. To test this concept, the antitumor activity of S-\n                    <jats:italic>trans<\/jats:italic>\n                    ,\n                    <jats:italic>trans<\/jats:italic>\n                    -farnesylthiosalicylic acid (FTS), a recently discovered Ras antagonist that dislodges Ras from its membrane-anchoring sites, was evaluated. The antitumor activity of FTS was assessed both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    in two independent SCID mouse xenotransplantation models of human melanoma expressing either wild-type Ras (cell line 518A2) or activated Ras (cell line 607B). We show that FTS (5\u201350 \u03bcM) reduces the amounts of activated N-Ras and wild-type Ras isoforms both in human melanoma cells and Rat-1 fibroblasts, interrupts the Ras-dependent extracellular signal-regulated kinase in melanoma cells, inhibits the growth of N-Ras-transformed fibroblasts and human melanoma cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    and reverses their transformed phenotype. FTS also causes a profound and statistically significant inhibition of 518A2 (82%) and 607B (90%) human melanoma growth in SCID mice without evidence of drug-related toxicity. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for human melanoma and possibly other tumors that either carry activated\n                    <jats:italic>ras<\/jats:italic>\n                    genes or rely on Ras signal transduction more heavily than nonmalignant cells.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.24.14019","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"14019-14024","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":80,"title":["Novel Ras antagonist blocks human melanoma growth"],"prefix":"10.1073","volume":"96","author":[{"given":"B.","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Dermatology, Division of General Dermatology, and Department of Clinical Pharmacology, Section of Experimental Oncology\/Molecular Pharmacology, University of Vienna, A-1090 Vienna, Austria; and Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69979 Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Schlagbauer-Wadl","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Division of General Dermatology, and Department of Clinical Pharmacology, Section of Experimental Oncology\/Molecular Pharmacology, University of Vienna, A-1090 Vienna, Austria; and Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69979 Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kahr","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Division of General Dermatology, and Department of Clinical Pharmacology, Section of Experimental Oncology\/Molecular Pharmacology, University of Vienna, A-1090 Vienna, Austria; and Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69979 Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Heere-Ress","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Division of General Dermatology, and Department of Clinical Pharmacology, Section of Experimental Oncology\/Molecular Pharmacology, University of Vienna, A-1090 Vienna, Austria; and Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69979 Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. X.","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Division of General Dermatology, and Department of Clinical Pharmacology, Section of Experimental Oncology\/Molecular Pharmacology, University of Vienna, A-1090 Vienna, Austria; and Department of Neurobiochemistry, The George S. 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