SOLID TUMOR

描述：（申请人描述）实体瘤项目支持 研究新的治疗方法和预测结果的癌症以外， 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程序， 假设被测试。具体目标1评估新的战略和新的 剂.通过剂量递增或更短的间期达到最佳剂量密度 将在生殖细胞肿瘤患者中测试治疗间隔或两者 和膀胱癌。新药，包括格尔德霉素（GDM）（ 干扰正常热休克蛋白90功能），一种新的抗真菌药（10-炔丙基-10- den 7-氨基蝶呤; PDX）和埃坡霉素衍生物（脱氧埃坡霉素B; dEPL-B）将在单药和联合II期试验中进行测试。超过 未来五年，小细胞和非小细胞肺癌（NSCLC）， 膀胱癌和头颈癌（H/N）将是模型系统。具体 目的2检验了这样一种假设，即药物针对已知的细胞靶点或与 推定的分化活性将是有效的抗癌疗法。在 为此，针对已知肽、神经节苷脂或碳水化合物的疫苗 抗原将是有效的免疫原性靶点。多价疫苗将 在临床试验之前进行开发和测试，以测试以下假设： 术后微小残留病的治疗可改善预后， 乳腺癌和前列腺癌患者的放疗和/或化疗 癌一种具有假定分化作用的组蛋白去乙酰化酶抑制剂 能力，pyroximide，将在乳腺癌和前列腺癌进行测试。在 具体目标3，新的生存和耐药性和毒性标志物将 追究比较基因组杂交将在 石蜡包埋的肿瘤组织，以检验高度扩增的 染色体获得区域将在耐药细胞中更频繁地发生， 使用乳腺癌、NSCLC和H/N癌作为 模型磁共振光谱学将检验 磷脂代谢预测H/N患者的肿瘤敏感性和/或结果 癌症和肝转移患者。有限抽样策略 将应用于PDX、GDM、dEPL-B和pyroximide的II期试验， 确定对联合用药和II期研究重要的药效学关系 审判本项目中研究的大多数新药剂都是新的 在MSKCC进行药物开发。在II期试验之后，III期试验 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.