ression of Receptors for Luteinizing Hormone-Releasing mone (LH-RH) in Prostate Cancers following Therapy

Download pose: In addition to their expression on pituitary cells, receptors for luteinizing hormone-releasing ne (LH-RH) are found on most prostate cancer cells. These tumoral LH-RH receptors mediate the cytotoxic effects of LH-RH analogs and are potential therapeutic targets. Although pituitary LH-RH ors are downregulated following prolonged exposure to LH-RH agonists, there is no evidence that ral receptors behave in a similar manner. To better characterize expression of tumoral LH-RH ors, specimens of prostate cancer from various cohorts of patients were analyzed. erimental Design: Surgical specimens were obtained from untreated patients with prostate cancer om patients with metastatic castration-resistant prostate cancer previously treated with bilateral ctomy. To address the possibility of receptor downregulation, two additional cohorts of patients ad been previously treated with LH-RH agonists were included. One group received neoadjuvant y prior to prostatectomy, and the other group was treated for metastatic disease with LH-RH sts and, at progression, required palliative resection of the prostate. Lymph node metastases from usly untreated patients were subjected to similar analysis. ults: Expression of LH-RH receptors was found in most specimens. The relative expression of receptor mRNA in untreated patients was greater in patients whose tumor had received a Gleason <8. clusions: LH-RH receptor expression persisted despite prolonged exposure to LH-RH agonists. findings support the concept of targeting cytotoxic LH-RH analogs to prostatic LH-RH receptors, These using these receptors to gain entry into cancer cells to deliver a hybridized cytotoxic moiety for the treatment of prostate cancer. Clin Cancer Res; 16(18); 4675–80. ©2010 AACR.