MOLECULAR ONCOLOGY PROGRAM PROJECT

分子肿瘤学计划项目(MOPP)的最终目标是在更好地了解肿瘤细胞存活和耐药性的基础上，开发更有效的人类癌症治疗方法。这一目标将通过对分子机制的原始实验室研究与创新临床试验的紧密结合来实现。为了实现这一目标，基础科学家和临床研究人员之间的合作对每个研究项目都是不可或缺的：MOPP包括三个组成部分的研究项目、三个核心和九个临床方案。所有的研究项目都将以骨髓瘤为范式或模型，研究肿瘤细胞存活和治疗反应的机制。在这个模型中所做的观察也将扩展到其他癌症，包括乳腺癌和卵巢癌。项目I将研究肿瘤微环境通过赋予细胞黏附介导的耐药性来影响药物反应的假说。骨髓瘤细胞系通过黏附改善对化疗药物和放射治疗的反应。项目II通过调节也会导致化疗耐药的细胞凋亡机制而发生恶性进展。这一假设将在骨髓瘤研究和乳腺癌新辅助化疗的II期临床试验中得到评估。拓扑异构酶I和II参与了对这些酶抑制剂的耐药性。实验室研究骨髓瘤、急性髓细胞白血病、非霍奇金淋巴瘤和慢性淋巴细胞性白血病以及某些实体瘤。组成项目的研究将得到三个核心的支持，包括行政核心、病理学核心和临床试验核心。这些紧密结合的癌症治疗实验室和临床研究的高度协作性将大大加强MOPP的研究项目。这些研究的结果将为肿瘤细胞杀伤和耐药的分子机制提供新的见解，这些机制将直接转化为更有效的癌症治疗。

The ultimate goal of the Molecular Oncology Program Project (MOPP) is to develop more effective therapies for human cancer based on a better mechanistic understanding of tumor cell survival and drug resistance. The goal will be pursued through close integration of original laboratory studies on molecular mechanisms with innovative clinical trials. To achieve this goal, collaborations between basic scientists and clinical investigators are integral to each research project: MOPP comprises three component research project, three cores, and nine clinical protocols. All the research projects will use myeloma as a paradigm, or model, to study mechanisms of tumor cell survival and treatment response. Observations made in this model will also be extended to other cancers, including breast and ovarian cancer. Project I will investigate the hypothesis that the tumor microenvironment influences drug response by conferring cell adhesion-mediated drug resistance. Myeloma cell lines by adhesion improves treatment response to chemotherapy drugs and radiation. Project II malignant progression through regulation of apoptotic mechanisms that also induce resistance to chemotherapy. This hypothesis will be evaluated in myeloma studies and a phase II clinical trial of neoadjuvant chemotherapy in breast alterations of topoisomerases I and II are involved in drug resistance to inhibitors of these enzymes. Laboratory studies myeloma, AML, NHL, and CLL, as well as certain solid tumors. Research in the component projects will be supported by three cores, including the Administrative Core, the Pathology Core, and the Clinical Trials Core. The MOPP research projects will e significantly enhanced by the highly collaborative nature of these closely integrated laboratory and clinical studies of cancer therapeutics. Results of these studies will provide new insights into the molecular mechanisms of tumor cell killing and drug resistance that will be directly translated into more effective cancer therapies.