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[Receptors for luteinizing hormone releasing hormone expressed on melanoma, renal cell carcinoma and non Hodgkin lymphoma can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone analogues].

AbstractAIMS:
Cytotoxic luteinizing hormone releasing hormone (LHRH) analogues AN-152 and AN-207 consist of [D-Lys6] LHRH linked to doxorubicin or its hyperactive derivate AN-201 and bind with high affinity to LHRH receptors. We evaluated the use of AN-207 and AN-201 in a nude mice model. In order to provide a rationale for the possible use of cytotoxic LHRH analogues in different malignancies we investigated the expression of LHRH-R in human renal cell carcinoma (RCC), melanoma and non Hodgkin's Lymphoma (NHL).
METHODS:
The expression of LHRH-R was examined in surgically removed human specimens of primary tumours and metastases from 37 RCC, 19 melanomas and 17 NHLs. In addition, human tumour cell lines expressing LHRH receptors were transplanted into nude mice and anti-tumour efficacy and systemic toxicity of AN-207 and its cytotoxic radical AN-201 were compared in various experiments.
RESULTS:
Positive staining for LHRH receptors was found in all of the RCC (37/37) and the melanoma specimens (19/19) as well as in 100% (10/10) of the NHLs. In in vivo experiments AN-207 significantly inhibited tumour growth while the cytotoxic radical alone was ineffective. Furthermore, side effects were reduced with targeted therapy.
CONCLUSIONS:
LHRH receptor expression was found to be very high in melanomas, RCCs and NHLs. Therefore targeted therapy with cytotoxic LHRH analogues may be a promising, novel therapy for advanced stages of these tumours. A first clinical trial with AN-152 was initiated recently in breast cancer patients.
AuthorsT Gaiser, J Rüschoff, A V Schally, G Keller, J B Engel
JournalVerhandlungen der Deutschen Gesellschaft fur Pathologie (Verh Dtsch Ges Pathol) Vol. 90 Pg. 186-92 ( 2006) ISSN: 0070-4113 [Print] Germany
Vernacular TitleDie Expression von LHRH-Rezeptoren im malignen Melanom, Nierenzellkarzinom und Non Hodgkin Lymphom--Bedeutung für eine neue rezeptorvermittelte Chemotherapie mit zytotoxischen LHRH-Analoga.
PMID17867596 (Publication Type: English Abstract, Journal Article)
Chemical References
  • Antineoplastic Agents
  • Receptors, LHRH
  • Doxorubicin
Topics
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Disease Models, Animal
  • Doxorubicin (therapeutic use)
  • Humans
  • Kidney Neoplasms (drug therapy, genetics, pathology)
  • Lymphoma, Non-Hodgkin (drug therapy, genetics, pathology)
  • Melanoma (drug therapy, genetics, pathology)
  • Neoplasm Metastasis
  • Receptors, LHRH (analysis, antagonists & inhibitors)

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