Musumeci Francesca, Greco Chiara, Grossi Giancarlo, Molinari Alessio, Schenone Silvia
Department of Pharmacy, University of Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
Cancers (Basel). 2018 Nov 9;10(11):430. doi: 10.3390/cancers10110430.
Ponatinib is a third line drug for the treatment of chronic myeloid leukemia patients, especially those that develop the gatekeeper mutation T315I, which is resistant to the first and the second line drugs imatinib, nilotinib, dasatinib and bosutinib. The compound was first identified as a pan Bcr-Abl and Src kinase inhibitor. Further studies have indicated that it is a multitargeted inhibitor that is active on FGFRs, RET, AKT, ERK1/2, KIT, MEKK2 and other kinases. For this reason, the compound has been evaluated on several cancers in which these kinases play important roles, including thyroid, breast, ovary and lung cancer, neuroblastoma, rhabdoid tumours and in myeloproliferative disorders. Ponatinib is also being tested in clinical trials to evaluate its activity in FLT3-ITD acute myelogenous leukemia, head and neck cancers, certain type of lung cancer, gastrointestinal stromal tumours and other malignancies. In this review we report the most recent preclinical and clinical studies on ponatinib in cancers other than CML, with the aim of giving a complete overview of this interesting compound.
波纳替尼是用于治疗慢性髓性白血病患者的三线药物，尤其适用于那些发生门卫突变T315I的患者，该突变对一线和二线药物伊马替尼、尼洛替尼、达沙替尼和博舒替尼具有抗性。该化合物最初被鉴定为一种泛Bcr-Abl和Src激酶抑制剂。进一步研究表明，它是一种多靶点抑制剂，对FGFRs、RET、AKT、ERK1/2、KIT、MEKK2和其他激酶具有活性。因此，该化合物已在这些激酶起重要作用的多种癌症中进行了评估，包括甲状腺癌、乳腺癌、卵巢癌和肺癌、神经母细胞瘤、横纹肌样肿瘤以及骨髓增殖性疾病。波纳替尼也正在进行临床试验，以评估其在FLT3-ITD急性髓性白血病、头颈癌、某些类型的肺癌、胃肠道间质瘤和其他恶性肿瘤中的活性。在本综述中，我们报告了关于波纳替尼在慢性粒细胞白血病以外的癌症中的最新临床前和临床研究，旨在全面概述这种有趣的化合物。
