Diagnostic Therapeutic Targets in Prostate Cancer

描述（由申请人提供）：通过鉴定可靠和高度特异性的新的血清学诊断标记，以及开发新的治疗策略和有效消除前列腺癌细胞的药物，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鉴定新的分子靶点来选择性杀死或选择性检测前列腺起源的癌细胞来实现。本项目旨在利用最近开发的功能强大的基因克隆方法、基于cDNA阵列的基因表达谱和合理设计的实验模型相结合，识别诊断和治疗应用的潜在基因靶点。使用特异性抑制剂和抗体来评估潜在候选物的诊断和治疗价值。Aim 1致力于在抑癌基因（PTEN, Rb， p53和p27）阴性控制的前列腺特异性基因编码的蛋白中鉴定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检测。这种方法是最近的一项工作的延伸，该工作将肿瘤特异性的PSA表达与p53的负调控联系起来。图2和图3用小分子表示细胞。它们是基于研究小组最近开发的两种新的遗传方法。通过结合实验和生物信息学标准收集的前列腺特异性基因序列表达文库的功能筛选，将分离特异性杀死前列腺癌细胞的遗传元件（特别关注激素不依赖型肿瘤）。对前列腺细胞生存能力至关重要的基因（evp基因）将被定义并用作选择抑制前列腺源性细胞生长的特定小分子的靶标，这些小分子将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.