摘要: |
There is no effective therapy to-date that can effectively cure prostate cancer bone metastasis. Systemic chemotherapy can be used to treatmetastatic prostate cancer, however, the tumors often will become resistant. Our studies suggested that a cell-surface protein called neuropilin-2 ishighly expressed in metastatic prostate cancer cells especially when they are in bone and is responsible for their ability to resist therapy. Based onour preliminary results, we hypothesized in the current proposal that a neuropilin-2 targeting drug in combination with chemotherapy should be aneffective treatment strategy for prostate cancer patients with bone metastasis. Recently, with the help of computer modeling-based screeningstrategy and supportive wet laboratory-based studies, we have identified a FDA approved drug, which can specifically block neuropilin-2. In thisproposal, we will test the potential of this drug in the combination with chemotherapy in preclinical mouse model of prostate cancer bonemetastasis. We will also study a blood-based biomarker, which will can indicate high neuropilin-2 expression in metastatic bone tissues. This markerwill thus help to stratify metastatic patients, who will be best suited for neuropilin-2 targeting drug therapy. Successful completion of the proposedproject will eventually lead to the anti-neuropilin-2 drug as a front-line therapy for the lethal metastatic prostate cancer. Since this anti-NRP2 drug isan FDA approved drug for other disease-specific uses, the detailed information about it regarding its pharmacology, formulation and potentialtoxicity to human is known. Re-purposing this drug to treat lethal prostate cancer can be done with ease. We expect within 5-8 year time period fromnow, the drug can complete the necessary clinical trials and can be integrated as a therapy for prostate cancer. |