Expression of receptors for Luteinizing Hormone-Releasing Hormone (LH-RH) in prostate cancers following therapy with LH-RH agonists

Stephen V. Liu, Andrew V. Schally, Debra Hawes, Shigang Xiong, Laden Fazli, Martin Gleave, Jie Cai, Susan Groshen, Frank Brands, Juergen Engel, Jacek Pinski

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36 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)4675-7680
Number of pages3006
JournalClinical Cancer Research
Volume16
Issue number18
DOIs
StatePublished - Sep 15 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Liu, S. V., Schally, A. V., Hawes, D., Xiong, S., Fazli, L., Gleave, M., Cai, J., Groshen, S., Brands, F., Engel, J., & Pinski, J. (2010). Expression of receptors for Luteinizing Hormone-Releasing Hormone (LH-RH) in prostate cancers following therapy with LH-RH agonists. Clinical Cancer Research, 16(18), 4675-7680. https://doi.org/10.1158/1078-0432.CCR-10-1113