APA
Click to copy
Su, Y., Vilgelm, A., Kelley, M., Hawkins, O. E., Liu, Y., Boyd, K., … Richmond, A. (2012). RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors. Clinical Cancer Research.
Chicago/Turabian
Click to copy
Su, Yingjun, A. Vilgelm, M. Kelley, Oriana E. Hawkins, Yan Liu, K. Boyd, S. Kantrow, et al. “RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors.” Clinical Cancer Research (2012).
MLA
Click to copy
Su, Yingjun, et al. “RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors.” Clinical Cancer Research, 2012.
BibTeX Click to copy
@article{yingjun2012a,
title = {RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors},
year = {2012},
journal = {Clinical Cancer Research},
author = {Su, Yingjun and Vilgelm, A. and Kelley, M. and Hawkins, Oriana E. and Liu, Yan and Boyd, K. and Kantrow, S. and Splittgerber, R. and Short, Sarah P. and Sobolik, T. and Zaja-Milatovic, Snjezana and Dahlman, K. and Amiri, K. and Jiang, A. and Lu, P. and Shyr, Y. and Stuart, D. and Levy, S. and Sosman, J. and Richmond, A.}
}
Purpose: The purpose of this preclinical study was to determine the effectiveness of RAF265, a multikinase inhibitor, for treatment of human metastatic melanoma and to characterize traits associated with drug response. Experimental Design: Advanced metastatic melanoma tumors from 34 patients were orthotopically implanted to nude mice. Tumors that grew in mice (17 of 34) were evaluated for response to RAF265 (40 mg/kg, every day) over 30 days. The relation between patient characteristics, gene mutation profile, global gene expression profile, and RAF265 effects on tumor growth, mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation, proliferation, and apoptosis markers was evaluated. Results: Nine of the 17 tumors that successfully implanted (53%) were mutant BRAF (BRAFV600E/K), whereas eight of 17 (47%) tumors were BRAF wild type (BRAFWT). Tumor implants from 7 of 17 patients (41%) responded to RAF265 treatment with more than 50% reduction in tumor growth. Five of the 7 (71%) responders were BRAFWT, of which 1 carried c-KITL576P and another N-RASQ61R mutation, while only 2 (29%) of the responding tumors were BRAFV600E/K. Gene expression microarray data from nonimplanted tumors revealed that responders exhibited enriched expression of genes involved in cell growth, proliferation, development, cell signaling, gene expression, and cancer pathways. Although response to RAF265 did not correlate with pERK1/2 reduction, RAF265 responders did exhibit reduced pMEK1, reduced proliferation based upon reduced Ki-67, cyclin D1 and polo-like kinase1 levels, and induction of the apoptosis mediator BCL2-like 11. Conclusions: Orthotopic implants of patient tumors in mice may predict prognosis and treatment response for melanoma patients. A subpopulation of human melanoma tumors responds to RAF265 and can be characterized by gene mutation and gene expression profiles. Clin Cancer Res; 18(8); 2184–98. ©2012 AACR.
