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性的新血清学标志物以及开发用于有效消除前列腺癌细胞的新治疗策略和药物，可以极大地促进前列腺癌治疗的进展。这两个目标都可以通过识别用于选择性杀死或选择性检测前列腺起源的癌细胞的新分子靶标来实现。本计划的目的是确定未来的诊断和治疗应用的基因靶点，使用最近开发的功能强大的基因克隆方法与cDNA阵列为基础的基因表达谱和合理设计的实验模型相结合。将使用特异性抑制剂和抗体评价潜在候选物的诊断和治疗价值。目的1从前列腺特异性基因编码的蛋白质中筛选新的候选前列腺肿瘤标志物，并设计前列腺癌的免疫诊断血清学方法。这种方法是最近工作的延伸，该工作将PSA表达的肿瘤特异性与p53的负调控联系起来。目的2和3通过小分子表示细胞。它们是基于研究小组最近开发的两种新的遗传学方法。通过对基于实验和生物信息学标准的组合收集的前列腺特异性基因序列的表达文库进行功能筛选，分离特异性杀伤前列腺癌细胞的遗传元件（特别关注非依赖于前列腺的肿瘤）。将定义前列腺细胞活力所必需的基因（EVP基因），并将其用作选择抑制前列腺来源细胞生长的特定小分子的靶标，这些小分子将用作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.