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1 November 2005 Minireview. Targeting Breast and Prostate Cancers Through Their Hormone Receptors
Carola Leuschner, William Hansel
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Abstract

A targeted treatment that effectively destroys human breast, prostate, ovarian, and testicular cancer cells that express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors has been developed. The treatment consists of a conjugate of a membrane-disrupting lytic peptide (Hecate, Phor14, or Phor21) and a 15-amino acid segment of the beta chain of CG. Because these conjugates act primarily by destroying cell membranes, their effects are independent of cell proliferation. The conjugates are relatively small molecules, are rapidly metabolized, and are not antigenic. In a series of independent experiments conducted in three different laboratories, the validity of the concept has been established, and it has been shown that the LH/CG receptor capacity of the cancer cells is directly related to the sensitivity of the lytic peptide conjugates. Sensitivity to the drugs can be increased by pretreating prostate or breast cancer cells with FSH or estradiol to up-regulate LH/CG receptors. A series of 23 in vivo experiments involving a total of 1630 nude mice bearing xenografts of human prostate or breast cancer cells showed convincingly that all three lytic peptide-betaCG compounds were highly effective in destroying tumors and reducing tumor burden. Hecate-betaCG was less effective in mice bearing ovarian epithelial cancer cell xenografts, but was highly effective in treating granulosa cell tumors in transgenic mice. In addition, Hecate-betaCG and Phor14-betaCG were highly effective in targeting and destroying prostate and breast cancer cell metastases in the presence or absence of the primary tumors. Although effective in vitro, neither Hecate nor Phor14 alone were effective in reducing primary tumor volume or burden in nude mice bearing prostate or breast cancer xenografts.

Carola Leuschner and William Hansel "Minireview. Targeting Breast and Prostate Cancers Through Their Hormone Receptors," Biology of Reproduction 73(5), 860-865, (1 November 2005). https://doi.org/10.1095/biolreprod.105.043471
Received: 4 May 2005; Accepted: 1 July 2005; Published: 1 November 2005
KEYWORDS
gonadotropin-releasing hormone
gonadotropin-releasing hormone receptor
human breast cancer
human chorionic gonadotropin
human prostate cancer
LH/CG receptors
luteinizing hormone
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