HOMING PEPTIDES FOR THE VASCULATURE IN PROSTATE

该部分将应用在项目负责人的实验室中开发的基于肽库的血管靶向，以描述前列腺肿瘤发生期间血管系统中的分子改变。将分离用于前列腺癌的血管和淋巴管系统的新肽，并将探索它们作为前列腺疾病的治疗靶向工具的效用。筛选的设计将有利于通常识别前列腺癌脉管系统的肽，而不是对个体前列腺癌模型具有选择性。这些肽的特异性将通过测试肽与来自小鼠和来自人类患者的正常和癌组织的结合来确定。将鉴定最有希望的肽的靶分子（“受体”），并制备针对受体的抗体。的肽 将测试如上所述鉴定和表征的肽-药物或抗体-药物偶联物以及针对其受体制备的抗体对前列腺癌脉管系统和肿瘤生长的作用，以及它们将肽-药物或抗体-药物偶联物递送至恶性前前列腺病变和前列腺癌的能力。从这些实验中出现的有希望的化合物将在临床前前列腺癌模型中进行测试，用于预防和治疗前列腺癌。从这项研究中将获得关于组织和肿瘤特异性脉管系统特化的新信息。用于预防前列腺癌发展和治疗前列腺癌的新疗法 可能会出现前列腺癌。

This component will apply peptide library-based vascular targeting developed in the project leader's laboratory to profile molecular alterations in vasculature during prostate tumorigenesis. New peptides for both the blood vessel and lymphatic vasculature of prostate cancer will be isolated and their utility as tools for therapeutic targeting of prostate diseases will be explored. The design of the screening will favor peptides that generally recognize prostate cancer vasculature, rather than being selective for an individual prostate cancer model. The specificity of these peptides will be ascertained by testing peptide binding to normal and cancerous tissues from mice and from human patients. The target molecules ('receptors") for the most promising peptides will be identified and antibodies will be prepared against the receptors. The peptides identified and characterized as described above and antibodies prepared against their receptors will be tested for their effects on prostate cancer vasculature and tumor growth, and their ability to deliver peptide-drug or antibody-drug conjugates to pre-malignant prostate lesions and prostate cancers. Promising compounds emerging from these experiments will be tested in pre-clinical prostate cancer models for prevention and treatment of prostate cancer. New information on tissue- and tumor-specific vasculature specialization will be gained from this study. New therapies for preventing the development of prostate cancer and for treating established prostate cancer may emerge.