Generation of a Novel Therapeutic for Prostate Cancer Bone Metastasis

DESCRIPTION (provided by applicant): Prostate cancer is the third most common form of cancer in the US with an estimated 186,320 new cases in 2008 and 28,660 associated deaths. There are no curative treatments for metastatic prostate cancer. The annual cost of treating prostate cancer in the US is approximately 8 billion dollars. The end points of this proposal are to generate a new drug candidate, CT400P, and demonstrate therapeutic activity in a model of prostate cancer bone metastasis. CT400 is an engineered form of FGF1 that is designed to broadly antagonize functions of FGFs including angiogenesis, tumor growth and tumor resistance to chemotherapy. CT400 has previously demonstrated efficacy in a model of breast cancer. A PEGylated form of CT400 (CT400P) will be generated to increase solubility, circulatory half-life and potentially decrease immunogenicity. The PEGylated form of CT400 will be selected based on possessing key CT400 activities and enhanced drug-like properties. Thus CT400P must maintain: 1) high affinity for FGFRs and lack of integrin binding, 2) efficient antagonism of FGF1 and FGF2- induced cell proliferation, and 3) efficient reversal of cancer cell chemoresistance. CT400P will then be tested for efficacy in a mouse model of prostate cancer bone metastasis. The pharmacokinetic profile and/or tissue half-life will be determined to develop a dosing schedule. CT400P will be administered therapeutically, subsequent to establishing tumor growth. The efficacy of CT400P will be determined primarily by measuring changes in tumor growth. Having demonstrated proof of concept in a prostate cancer model CT400P will progress toward becoming a new therapeutic to treat prostate cancer and ultimately other types of cancers. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to generate a new drug candidate and demonstrate therapeutic activity in a model of prostate cancer. It is anticipated that this therapeutic will be developed to treat prostate cancer for which there are 190,000 new cases with 29,000 associated deaths annually in the US. This new drug may ultimately be used to treat several types of cancer.