Preliminary Study of Mycograb and Docetaxel in Advanced Breast Cancer

Combination therapies that incorporate new agents have demonstrated the potential to improve outcome for patients with metastatic breast carcinoma. Docetaxel has been shown to be a very active drug in breast cancer, and anthracycline-based chemotherapy combinations represent the most active form of therapy generating objective response rates of between 40-70%. Mycograb® was most effective in breast carcinoma cell lines in combination with cisplatin, docetaxel and anthracyclines (doxorubicin, daunorubicin). We propose that Mycograb® binds to hsp90, inhibiting hsp90 chaperone functioning and resulting in the destabilization of key proteins including estrogen/steroid receptors, nitric oxide synthase, ras1, MAP (Mitogen-activated protein) kinase, Src, Erb-B2,(erythroblastic leukemia viral oncogene homolog 2) HER(human estrogen receptor) kinases and EGFR (epidermal grown factor receptor). Over expression of HER2 receptors are observed in malignancies such as breast cancer and reportedly have been associated with resistance to chemotherapeutic agents. Both maturing and fully mature forms of the receptor depend on hsp90 association for stability. Inhibition of hsp90 function down regulates AKT kinase and Src kinase which are non-receptor kinase. Therefore, Mycograb® may be of use in estrogen dependent and hormone independent breast cancers. Mycograb® has been demonstrated to have anti-tumor activity in cell culture. The 50% cytotoxicity of Mycograb® on its own is 50 Combination therapies that incorporate new agents have demonstrated the potential to improve outcome for patients with metastatic breast carcinoma. Docetaxel has been shown to be a very active drug in breast cancer, and anthracycline-based chemotherapy combinations represent the most active form of therapy generating objective response rates of between 40-70%. Mycograb® was most effective in breast carcinoma cell lines in combination with cisplatin, docetaxel and anthracyclines (doxorubicin, daunorubicin). We propose that Mycograb® binds to hsp90, inhibiting hsp90 chaperone functioning and resulting in the destabilization of key proteins including estrogen/steroid receptors, nitric oxide synthase, ras1, MAP kinase, Src, Erb-B2, HER kinases and EGFR. Overexpression of HER2 receptors are observed in malignancies such as breast cancer and reportedly have been associated with resistance to chemotherapeutic agents. Both maturing and fully mature forms of the receptor depend on hsp90 association for stability. Inhibition of hsp90 function down regulates AKT kinase and Src kinase which are non-receptor kinase. Therefore, Mycograb® may be of use in estrogen dependent and hormone independent breast cancers. Mycograb® has been demonstrated to have anti-tumor activity in cell culture. The 50% cytotoxicity of Mycograb® on its own is 50 µg/ml (MCF7 \[Breast cancer cell line designation\]). Mycograb® in combination with docetaxel, doxorubicin and cisplatin and Herceptin increased the cytotoxicity in breast cancer cells. It is appropriate to evaluate the apparent tumor response and survivor benefits resulting from the addition of Mycograb® to a docetaxel containing chemotherapy regimen in metastatic or recurrent breast cancer patients. (MCF7). Mycograb® in combination with docetaxel, doxorubicin and cisplatin and Herceptin increased the cytotoxicity in breast cancer cells. It is appropriate to evaluate the apparent tumor response and survivor benefits resulting from the addition of Mycograb® to a docetaxel containing chemotherapy regimen in metastatic or recurrent breast cancer patients.