TY - JOUR
T1 - Targeting melanoma with NT157 by blocking Stat3 and IGF1R signaling
AU - Flashner-Abramson, E.
AU - Klein, S.
AU - Mullin, G.
AU - Shoshan, E.
AU - Song, R.
AU - Shir, A.
AU - Langut, Y.
AU - Bar-Eli, M.
AU - Reuveni, H.
AU - Levitzki, A.
N1 - Funding Information:
This study was supported by an ERC Advanced Grant (No. 249898) to AL by the NIH Skin Cancer SPORE p50 (No. CA093459), by four grants from the Office of the Chief Scientist in the Ministry of Industry, Trade and Labor of Israel to NovoTyr (HR, 2005-2012) and by Algen Biopharmaceuticals Ltd.
Publisher Copyright:
© 2016 Macmillan Publishers Limited.
PY - 2016/5/19
Y1 - 2016/5/19
N2 - It is well known that specific signal transduction inhibitors rarely suffice as anti-cancer agents. In most cases, tumors possess primary drug resistance due to their inherent heterogeneity, or acquire drug resistance due to genomic instability and acquisition of mutations. Here we expand our previous study of the novel compound, NT157, and show that it acts as a dual-targeting agent that invokes the blockage of two signal transduction pathways that are central to the development and maintenance of multiple human cancers. We show that NT157 targets not only IGF1R-IRS1/2, as previously reported, but also the Stat3 signaling pathway and demonstrates remarkable anti-cancer characteristics in A375 human melanoma cells and in a metastatic melanoma model in mice.
AB - It is well known that specific signal transduction inhibitors rarely suffice as anti-cancer agents. In most cases, tumors possess primary drug resistance due to their inherent heterogeneity, or acquire drug resistance due to genomic instability and acquisition of mutations. Here we expand our previous study of the novel compound, NT157, and show that it acts as a dual-targeting agent that invokes the blockage of two signal transduction pathways that are central to the development and maintenance of multiple human cancers. We show that NT157 targets not only IGF1R-IRS1/2, as previously reported, but also the Stat3 signaling pathway and demonstrates remarkable anti-cancer characteristics in A375 human melanoma cells and in a metastatic melanoma model in mice.
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U2 - 10.1038/onc.2015.229
DO - 10.1038/onc.2015.229
M3 - Article
C2 - 26119932
AN - SCOPUS:84933566448
SN - 0950-9232
VL - 35
SP - 2675
EP - 2680
JO - Oncogene
JF - Oncogene
IS - 20
ER -