Targeting breast cancer metastasis with inhibitors of Id-1

描述(由申请人提供)：侵袭性乳腺癌的转移是一种毁灭性的最终致命的疾病。目前用于治疗乳腺癌转移的一线药物主要针对肿瘤生长。这些药物只能适度增加侵袭性转移性癌症患者的存活率，并有显著的副作用。目前，还没有可用的治疗方案可以特异性和有效地抑制肿瘤的侵袭和转移。因此，需要新的药物策略来治疗这种慢性、致命和不可治愈的疾病。我们治疗侵袭性乳腺癌的策略是基于减少ID-1的表达。ID-1是乳腺癌和其他癌症侵袭和转移潜力的关键调节因子。在这个第一阶段的提案中，我们的重点将放在我们的先导化合物的优化上，以发现一个或多个下调ID-1表达的类似物，从而抑制乳腺癌细胞的侵袭和转移。我们还将对这些化合物进行优化，使它们显示出良好的ADME-TOX图谱。这项建议的最终目标是通过下调ID-1的表达来开发一种治疗转移性人类乳腺癌的新方法。

DESCRIPTION (provided by applicant): Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition. The current first- line agents which are used to treat breast cancer metastasis primarily target tumor growth. These drugs produce only modest increases in survival in patients with aggressive metastatic cancers and have significant side effects. Currently, there are no available treatment options that can specifically and effectively inhibit tumor invasion and metastasis. Therefore, novel drug strategies are needed to treat this chronic, fatal and incurable condition. Our therapeutic strategy for the treatment of aggressive breast cancer is based on reducing Id-1 expression. Id-1 is a key regulator of the invasive and metastatic potential of breast and additional cancers. In this Phase I proposal our focus will be on the optimization of our lead compound to discover one or more analogs that down-regulate Id-1 expression and consequently inhibit breast cancer cell invasion and metastasis. We will also optimize these compounds so that they display a favorable ADME-Tox profile. The ultimate goal of this proposal is to develop a novel therapeutic approach for the treatment of metastatic human breast cancers by down-regulation of Id-1.