Targeted chemotherapy of endometrial, ovarian and breast cancers with cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH)
Archives of Gynecology and Obstetrics, 05/10/2012
Engel JB et al. – EP–100 is a membrane–disrupting peptide targeted to LHRH receptors, which is undergoing early clinical studies in ovarian cancer patients.
- 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–Lys6]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.