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JMR-132 is an antagonist of growth hormone releasing hormone (GHRH) which binds to splice variants of the GHRH- receptors, found on a variety of tumors including human breast, prostate, ovarian and endometrial cancers. The activity of this analog was demonstrated in various experimental models of human cancers. Here we report on the antitumor activity of JMR-132 in MX-1 human experimental, doxorubicin-resistant breast cancers. In addition, we evaluated the anti-proliferative effect of JMR-132 in combination with docetaxel, which is frequently used for the treatment of early and metastatic breast cancer.

We found binding sites for GHRH in the MX-1 human breast cancer cell line. The treatment of nude mice bearing MX-1 xenografts with JMR-132 at the dose of 10 µg/day s.c. significantly (p<0.05) inhibited tumor growth, as shown by a 62.9% decrease in tumor volume and 47.8% reduction in tumor weight. Docetaxel at a single dose of 20 mg/kg i.p. significantly reduced tumor volume and weight by 74.1% and 58.6 %, respectively. Combination treatment with JMR-132 and docetaxel led to growth arrest of most MX-1 tumors, evidenced by an inhibition of tumor volume and weight by 97.7 and 95.6 %, respectively (p<0.001). Since no vital cancer cells were detected in some of the excised tumors, total regression of the tumors was achieved in some cases. Our results demonstrate that GHRH antagonist JMR-132 inhibits doxorubicin resistant in MX-1 human breast cancers and induces growth arrest or total regression when combined with docetaxel chemotherapy. Consequently JMR-132 could provide a new therapeutic approach to the treatment of early and metastatic breast cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA