HUMAN CANCER METASTASIS--BIOLOGY AND TREATMENT

在远离原发灶的器官出现转移 肿瘤是癌症最具破坏性的方面。少校 治疗已确定的转移瘤的障碍很可能是 它们的生物异质性是由连续的 肿瘤的进化是造成多重差异的原因 即存在于单个转移的肿瘤细胞之间。到目前为止， 大多数关于转移生物学的数据都是从 来自对啮齿动物肿瘤的研究。现在有必要延长 我们对相关人类肿瘤系统的研究。 我的长期目标是了解 调节人类肿瘤的转移扩散和 发展生物异质性，开发新的生物多样性 肿瘤转移的防治途径 人类。在接下来的几年里，我将调查 新分离的人类肿瘤中的转移异质性。 转移扩散的具体模式也将在 与肿瘤细胞的性质和肿瘤的性质的关系 寄主微环境。转移和非转移 亚群将从人类肿瘤和 肿瘤进展中的遗传和表观遗传机制 并将对转移情况进行调查。 Nepolasum的生物多样性意味着成功的 转移瘤的治疗将需要彻底摧毁所有 癌细胞。因此，肿瘤学家面临的挑战是 设计一种根除少数肿瘤细胞的新方法 抵制传统疗法的人。这样的方法将会有 为了绕过肿瘤的异质性问题和 出现耐药变异的肿瘤细胞。研究 来自我的实验室和其他许多人的建议是适当的 激活的巨噬细胞可以满足这些苛刻的标准， 因此，提供了一种生物方法来摧毁少数人 但致命的肿瘤细胞可以抵抗或逃脱传统疗法。 因此，我研究的第二个主要目标是研究 巨噬细胞在肿瘤发病机制中的作用 转移，设计全身激活的方法 巨噬细胞，并阐明其机制 杀瘤巨噬细胞区分致瘤和致瘤 非致瘤细胞。

The emergence of metastases in organs distant from the primary tumor is the most devastating aspect of cancer. The major obstacle for treatment of established metastaes could well be their biologic heterogeneity which results from the continuous evolution of tumors and is responsible for the multiple differences that exist among tumor cells of a single metastasis. To date, most of the data on the biology of metastasis have been derived from studies with rodent neoplasms. It is now necessary extend our investigations into relevant human tumor systems. My long-term goals are to understand the mechanisms that regulate the metastatic spread of human neoplasms and the development of biologic heterogeneity in order to develop new approaches to the prevention and treatment of metastasis in humans. In the coming years, I will investigate the extent of metastatic heterogeneity in freshly isolated human neoplasms. Specific patterns of metastatic spread will also be studied in relation to properties of the neoplastic cells and the nature of the host microenvironment. Metastatic and nonmetastatic subpopulations will be selected from human neoplasms and the genetic and epigenetic mechanisms involved in tumor progression and metastasis will be investigated. The biologic diversity of nepolasms implies that the successful treatment of metastasis will require the total destruction of all cancer cells. The challenge to the oncologist is, therefore, to devise a new approach for the eradication of the few tumor cells that resist conventional therapies. Such an approach would have to circumvent the problem of neoplastic heterogeneity and the emergence of treatment-resistant variant tumor cells. Studies from my laboratory and many others suggest that appropriately activated macrophages can meet these demanding criteria and, thus, provide a biological approach to the destruction of the few but fatal tumor cells that resist or escape conventional therapies. For this reason, the second major goal of my research is to study the role of the macrophage in the pathogenesis of cancer matastasis, to devise methods for systemic activation of macrophages, and to elucidate the mechanisms by which tumoricidal macrophages discriminate between tumorigenic and nontumorigenic cells.