Expression of Receptors for Luteinizing Hormone-Releasing Hormone (LH-RH) in Prostate Cancers following Therapy with LH-RH Agonists

S. V. Liu, A. V. Schally, D. Hawes, S. Xiong, L. Fazli, M. Gleave, J. Cai, S. Groshen, F. Brands, J. Engel, J. Pinski
2010 Clinical Cancer Research  
Purpose: In addition to their expression on pituitary cells, receptors for luteinizing hormone-releasing hormone (LH-RH) are found on most prostate cancer cells. These tumoral LH-RH receptors mediate the direct cytotoxic effects of LH-RH analogs and are potential therapeutic targets. Although pituitary LH-RH receptors are downregulated following prolonged exposure to LH-RH agonists, there is no evidence that tumoral receptors behave in a similar manner. To better characterize expression of
more » ... expression of tumoral LH-RH receptors, specimens of prostate cancer from various cohorts of patients were analyzed. Experimental Design: Surgical specimens were obtained from untreated patients with prostate cancer and from patients with metastatic castration-resistant prostate cancer previously treated with bilateral orchiectomy. To address the possibility of receptor downregulation, two additional cohorts of patients who had been previously treated with LH-RH agonists were included. One group received neoadjuvant therapy prior to prostatectomy, and the other group was treated for metastatic disease with LH-RH agonists and, at progression, required palliative resection of the prostate. Lymph node metastases from previously untreated patients were subjected to similar analysis. Results: Expression of LH-RH receptors was found in most specimens. The relative expression of LH-RH receptor mRNA in untreated patients was greater in patients whose tumor had received a Gleason score <8. Conclusions: LH-RH receptor expression persisted despite prolonged exposure to LH-RH agonists. These findings support the concept of targeting cytotoxic LH-RH analogs to prostatic LH-RH receptors, 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. Prostate cancer is the most common malignancy in men aside from skin cancer and is the second leading cause of cancer-related death (1); thus, prostate cancer creates a substantial public health burden. For patients with advanced prostate cancer, the cornerstone of therapy is androgen ablation through hormonal manipulation (2), either surgical, with bilateral orchiectomy, or medical, with the use of luteinizing hormone-releasing hormone (LH-RH) agonists. The two approaches are clinically equivalent,
doi:10.1158/1078-0432.ccr-10-1113 pmid:20670943 fatcat:gnlkz74fabd3tosfxul6ildvrm