Targeting the roots of cancer metastasis and therapy resistance

尽管在过去的二十年里取得了很大的进步，癌症仍然是一种经常致命的疾病。即使在今天，接受了包括靶向药物和免疫疗法在内的现代治疗方案的癌症患者中，只有大约30%的人长期缓解。癌症中最致命的步骤是转移，90%的癌症相关死亡都是由转移和治疗阻力造成的。这些事实表明，开发新的治疗策略的压力很大。在过去的20年里，我的研究促进了概念的进步，并确定了肿瘤向转移和治疗耐药发展过程中的新的分子联系。My和其他团队的工作表明，异种肿瘤中的一小部分癌细胞负责转移、治疗抵抗和疾病复发。这些癌细胞是高度可塑性的，并瞬时激活胚胎EMT(上皮-间充质转化)程序。拟议项目的目标是从分子上表征到目前为止，高度可塑性癌细胞中的这一“不可靶向”部分，从而支持开发新的治疗策略，以对抗治疗抵抗和转移。

Despite great progress in the last two decades, cancer is still an often deadly disease. Even today only about 30% of cancer patients, who received modern treatment regimens including targeted drugs and immunotherapy respond with long-term remission. The most fatal steps in cancer are metastasis, which is responsible for >90% of cancer-associated death, and therapy resistance. These facts demonstrate the high pressure to develop novel therapeutic strategies. My research over the last 20 years contributed to conceptual advance and the identification of novel molecular links in tumor progression towards metastasis and therapy resistance. The work of my and other groups demonstrated that a fraction of cancer cells within a heterogenous tumor is responsible for metastasis, therapy resistance and disease relapse. These cancer cells are highly plastic and transiently activate the embryonic embryonic EMT (epithelial-mesenchymal transition)-program. The goal of the proposed project is to molecularly characterize this until now “untargetable” fraction of highly plastic cancer cells, thereby supporting the development of novel therapeutic strategies against therapy resistance and metastasis.