Targeted chemotherapy of endometrial, ovarian and breast cancers with cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH)
Targeted chemotherapy of endometrial, ovarian and breast cancers with cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH)
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DOI：
10.1007/s00404-012-2335-1
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发表时间：
2012-08-01
影响因子：
2.6
通讯作者：
Ortmann, O.
中科院分区：
文献类型：
--
作者：
Engel, J. B.;Schally, A. V.;Ortmann, O.
促黄体生成素释放激素受体（LHRH）在大约80%的人类子宫内膜癌和卵巢癌中表达，在包括三阴性乳腺癌在内的乳腺癌中占50%以上。除垂体和生殖器官外，没有其他器官或造血干细胞表达LHRH （GnRH）受体。因此，这些受体可以被视为癌症治疗中个性化医学方法的理想靶点。aez -108（以前称为AN-152）中，doxorubin与LHRH激动剂[d-Lys(6)]LHRH连接，似乎是临床开发后期最先进的化合物。妇科癌症患者的I期和II期临床试验结果显示，即使在高度预处理的患者中，抗癌活性也没有任何心脏毒性。因此，aaes -108正被考虑用于三阴性乳腺癌的II期试验和lhrh受体阳性的晚期子宫内膜癌的III期研究。EP-100是一种靶向LHRH受体的膜破坏肽，目前正在卵巢癌患者中进行早期临床研究。
Receptors luteinizing hormone-releasing hormone (LHRH) are expressed in about 80 % of human endometrial and ovarian cancers and account for more than 50 % of breast cancers including triple negative breast cancers. Apart from the pituitary and reproductive organs, no other organs or hematopoietic stem cells express LHRH (GnRH) receptors. Thus, these receptors can be regarded as an ideal target for a personalized medicine approach in cancer therapy. AEZS-108 (formerly known as AN-152) in which doxorubin is linked to the LHRH agonist [d-Lys(6)]LHRH, appears to be the most advanced compound in late stage clinical development. Results of phase I and phase II clinical trials in patients with gynecological cancers demonstrated anticancer activity without any cardiotoxicity even in highly pretreated patients. AEZS-108 is therefore being considered for phase II trials in triple negative breast cancers and phase III studies in advanced endometrial cancers positive for LHRH-receptor. EP-100 is a membrane-disrupting peptide targeted to LHRH receptors, which is undergoing early clinical studies in ovarian cancer patients.