Diagnostic Therapeutic Targets in Prostate Cancer

描述(由申请人提供)：通过鉴定用于诊断的可靠和高度特异的新的血清学标记，以及开发有效消除前列腺癌细胞的新的治疗策略和药物，可以极大地促进前列腺癌的治疗进展。这两个目标都可以通过识别选择性杀伤或选择性检测前列腺癌来源的癌细胞的新分子靶点来实现。本计划旨在利用最近开发的功能强大的基因克隆方法与基于基因表达谱阵列的基因表达谱和合理设计的实验模型相结合，识别用于诊断和治疗应用的预期基因靶点。未来候选者的诊断和治疗价值将使用特定的抑制剂和抗体进行评估。目的1致力于从抑癌基因(PTEN、Rb、p53和p27)阴性控制的前列腺特异性基因编码的蛋白质中寻找新的候选前列腺癌标志物，并设计前列腺癌的免疫诊断血清学方法。这一方法是最近一项工作的延伸，该工作将PSA表达的肿瘤特异性与其受P53的负调控联系起来。目标2和目标3用小分子代表细胞。它们是基于研究团队最近开发的两种新的遗传方法。通过结合实验和生物信息学标准收集的前列腺特异基因序列表达文库的功能筛选，将分离出专门杀死前列腺癌细胞(特别是激素非依赖性肿瘤)的遗传因素。前列腺细胞存活所必需的基因(EVP基因)将被定义并用作靶点，以选择抑制前列腺癌来源细胞生长的特定小分子，作为前列腺癌治疗的原型新药。

DESCRIPTION (provided by applicant): Progress in curing prostate cancer could be greatly facilitated by identification of reliable and highly specific new serological markers for diagnostics and development of new therapeutic strategies and pharmaceuticals for effective elimination of prostate cancer cells. Both goals could be achieved through identification of new molecular targets for selective killing or selective detection of cancer cells of prostate origin. The present program is aimed at identification of prospective gene targets for both diagnostic and therapeutic applications using a combination of recently developed powerful functional gene cloning methodologies with cDNA array-based gene expression profiling and rationally designed experimental models. Diagnostic and therapeutic value of prospective candidates will be evaluated using specific inhibitors and antibodies. Aim 1 is devoted to identification of new candidate prostate tumor markers among proteins encoded by prostate-specific genes that are under negative control of tumor suppressor genes (PTEN, Rb, p53 and p27) followed by designing immunodiagnostic serological assay for prostate cancer. This approach is an extension of a recent work that linked tumor specificity of PSA expression with its negative regulation by p53. Aims 2 and 3 represent cells by small molecules. They are based on two new genetic methodologies recently developed by research the research team. Genetic elements specifically killing prostate carcinoma cells (with specific focus on hormone-independent tumors) will be isolated by functional screening of expression libraries of prostate-specific gene sequences collected based on a combination of experimental and bioinformatics-based criteria. Genes essential for viability of prostate cells (EVP-genes) will be defined and used as targets for selection of specific small molecules inhibiting growth of cells of prostate origin that will serve as prototype new drugs for prostate cancer treatment.