Santoni Matteo, Massari Francesco, Del Re Marzia, Ciccarese Chiara, Piva Francesco, Principato Giovanni, Montironi Rodolfo, Santini Daniele, Danesi Romano, Tortora Giampaolo, Cascinu Stefano
Polytechnic University of the Marche Region, Medical Oncology, AOU Ospedali Riuniti , via Conca 71, 60126 Ancona , Italy +39 0715964263 ; +39 0715964269 ;
Expert Opin Investig Drugs. 2015 Jun;24(6):809-24. doi: 10.1517/13543784.2015.1020370. Epub 2015 Mar 7.
Signal transducer and activator of transcription 3 (STAT3) mediates the expression of a variety of genes in response to cell stimuli and thus plays a key role in several cellular processes such as cell growth and apoptosis. Deregulation of the STAT3 activity has been shown in many malignancies, including breast, head and neck, prostate, pancreas, ovarian and brain cancers and melanoma. Thus, STAT3 may represent an ideal target for cancer therapy.
The authors review recent data on the role of STAT3 in tumor initiation and progression, as well as the ongoing clinical trials in cancer patients. The content includes information derived from trial databases, regulatory authorities and scientific literature.
Targeting STAT3 activation leads to the inhibition of tumor growth and metastasis both in vitro and in vivo without affecting normal cells; this suggests that STAT3 could be a valid molecular target for cancer therapy. Extensive clinical research is trying to find anti-STAT3 agents with high single-agent activity. The identification and development of novel drugs that can target deregulated STAT3 activation effectively is both a scientific and clinical challenge that needs to be addressed in the near future.
信号转导及转录激活因子3(STAT3)介导多种基因在细胞受到刺激时的表达,因此在细胞生长和凋亡等多个细胞过程中发挥关键作用。STAT3活性失调在许多恶性肿瘤中都有表现,包括乳腺癌、头颈癌、前列腺癌、胰腺癌、卵巢癌、脑癌和黑色素瘤。因此,STAT3可能是癌症治疗的理想靶点。
作者回顾了关于STAT3在肿瘤起始和进展中的作用的最新数据,以及正在进行的癌症患者临床试验。内容包括来自试验数据库、监管机构和科学文献的信息。
靶向STAT3激活在体外和体内均能抑制肿瘤生长和转移,而不影响正常细胞;这表明STAT3可能是癌症治疗的有效分子靶点。广泛的临床研究正在努力寻找具有高单药活性的抗STAT3药物。有效靶向失调的STAT3激活的新型药物的鉴定和开发是一个科学和临床挑战,需要在不久的将来加以解决。