SOLID TUMOR

描述：(申请者描述)实体肿瘤项目支持 其他癌症的新治疗方法和预后预测因素的研究 白血病和淋巴瘤。三个具体目标侧重于单一和 使用特定恶性肿瘤作为模型系统的组合计划 假设得到了检验。具体目标1评估新战略和小说 探员们。通过剂量递增或更短的间隔实现最佳剂量密度 将在生殖细胞肿瘤患者中测试治疗间隔，或两者兼而有之 和膀胱癌。新药，包括格尔达那霉素(GDM)(它 干扰正常HSP90功能)，一种新的安非他明(10-丙叉基-10-丙叉基-10-丙交酯) DEN7~nnlinopterin；PDX)和环氧苯丙酮衍生物(去氧泊硫酮B； DEPL-B)将在单剂和联合II期试验中进行测试。完毕 未来五年，小细胞和非小细胞肺癌(NSCLC)， 膀胱癌和头颈癌(H/N)将成为模型系统。特定的 AIM 2测试了一种假设，即药物针对已知的细胞靶点或与 推测的分化活性将是有效的抗癌治疗。在……里面 为了达到这个目的，针对已知肽、神经节苷脂或碳水化合物的疫苗 抗原将成为有效的免疫原性靶点。一种多价疫苗将 在临床试验之前进行开发和测试，以验证以下假设 随着术后微小残留疾病的治疗，结果会有所改善， 乳腺癌和前列腺癌患者的放射治疗和/或化疗 癌症。一种具有可能分化作用的组蛋白脱乙酰酶抑制剂 能力，吡咯胺，将在乳腺癌和前列腺癌中进行测试。在……里面 具体目标3，新的生存、耐药和毒性标志物将 被调查。比较基因组杂交将在 石蜡包埋的肿瘤组织来验证高度扩增的假设 在耐药患者中，染色体获得区将更频繁地出现 使用乳腺癌、非小细胞肺癌和H/N癌的肿瘤比使用药物敏感的肿瘤 模特们。磁共振波谱学将检验这一假说 磷脂代谢异常可预测H/N患者的肿瘤敏感性和/或预后 在癌症和肝转移患者中。有限抽样策略 将在PDX、GDM、DEPL-B和吡咯胺的第二阶段试验中应用，以 确定对联合和第二阶段重要的药效学关系 审判。这个项目中要研究的大多数新试剂都是新的 在MSKCC进行药物开发。在第二阶段试验之后，第三阶段试验 将在适当的情况下进行。

DESCRIPTION: (Applicant's Description) The Solid Tumor Project supports investigation of new therapy and predictors of outcome for cancers other than leukemia and the Lymphomas. Three specific aims focus on single and combination programs using specific malignancies as model systems on which hypotheses are tested. Specific Aim 1 evaluates new strategies and novel agents. Optimal dose-density achieved through dose escalation or shorter inter treatment intervals, or both, will be tested in patients with germ cell tumors and bladder cancer. Novel drugs, including the geldanamycins (GDM) (which interfere with normal hsp90 function), a new antifol (10-propargyl-10- den7~nnlinopterin; PDX), and an epothilone derivative (desoxyepothilone B; dEPL-B) will be tested in single-agent and combination Phase II trials. Over the next five years, small cell and non-small cell lung cancer (NSCLC), bladder cancer, and head and neck cancer (H/N) will be model systems. Specific Aim 2 tests the hypothesis that drugs aimed at known cellular targets or with putative differentiating activity will be effective anticancer therapy. In this aim, vaccines aimed at known peptide, ganglioside, or carbohydrate antigens will be effective immunogenstigenic target. A polyvalent vaccine will be developed and tested prior to clinical trials to test the hypothesis that outcome will improve with treatment of minimal residual disease after surgery, radiation therapy, and/or chemotherapy in patients with breast and prostate cancer. An histone deacetylase inhibitor with putative differentiating capability, pyroximide, will be tested in breast and prostate cancer. In Specific Aim 3, new markers of survival and drug resistance and toxicity will be investigated. Comparative genomic hybridization will be performed on paraffin-embedded tumor tissue to test the hypothesis that highly amplified regions of chromosomal gain will occur more frequently in drug-resistant tumors than drug-sensitive tumors using breast; NSCLC, and H/N cancer as models. Magnetic resonance spectroscopy will test the hypothesis that changes in phospholipid metabolism predicts tumor sensitivity and/or outcome in H/N cancer and in patients with hepatic metastases. Limited sampling strategies will be applied across Phase II trials of PDX, GDM, dEPL-B, and pyroximide to determine pharmacodynamic relationships important to combination and Phase II trials. Most new agents to be studied in this project are the result of new drug development conducted at MSKCC. After Phase II trials, Phase III triais will be conducted if appropriate.