Senses Kerem M, Ghasemi Mehdi, Akbar Muhammad W, Isbilen Murat, Fallacara Anna L, Frankenburg Shoshana, Schenone Silvia, Lotem Michal, Botta Maurizio, Gure Ali O
Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey.
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
Medchemcomm. 2017 Jan 1;8(1):88-95. doi: 10.1039/C6MD00466K. Epub 2016 Oct 27.
Transcriptomic phenotypes defined for melanoma have been reported to correlate with sensitivity to various drugs. In this study, we aimed to define a minimal signature that could be used to distinguish melanoma sub-types , and to determine suitable drugs by which these sub-types can be targeted. By using primary melanoma cell lines, as well as commercially available melanoma cell lines, we find that the evaluation of MLANA and INHBA expression is as capable as one based on a combined analysis performed with genes for stemness, EMT and invasion/proliferation, in identifying melanoma subtypes that differ in their sensitivity to molecularly targeted drugs. Using this approach, we find that 75% of melanoma cell lines can be treated with either the MEK inhibitor AZD6244 or the HSP90 inhibitor 17AAG.
据报道，为黑色素瘤定义的转录组表型与对各种药物的敏感性相关。在本研究中，我们旨在定义一个可用于区分黑色素瘤亚型的最小特征，并确定能够靶向这些亚型的合适药物。通过使用原发性黑色素瘤细胞系以及市售的黑色素瘤细胞系，我们发现，在识别对分子靶向药物敏感性不同的黑色素瘤亚型方面，评估MLANA和INHBA的表达与基于干性、上皮-间质转化（EMT）和侵袭/增殖相关基因的联合分析同样有效。使用这种方法，我们发现75%的黑色素瘤细胞系可以用MEK抑制剂AZD6244或HSP90抑制剂17AAG进行治疗。
