Kobelt Dennis, Dahlmann Mathias, Dumbani Malti, Güllü Nazli, Kortüm Benedikt, Vílchez Miguel E Alberto, Stein Ulrike, Walther Wolfgang
Department Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Moelcular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125 Berlin, Germany.
German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Cancers (Basel). 2020 Jun 3;12(6):1454. doi: 10.3390/cancers12061454.
Metastasis represents the most lethal attribute of cancer and critically limits successful therapies in many tumor entities. The clinical need is defined by the fact that all cancer patients, who have or who will develop distant metastasis, will experience shorter survival. Thus, the ultimate goal in cancer therapy is the restriction of solid cancer metastasis by novel molecularly targeted small molecule based therapies. Biomarkers identifying cancer patients at high risk for metastasis and simultaneously acting as key drivers for metastasis are extremely desired. Clinical interventions targeting these key molecules will result in high efficiency in metastasis intervention. In result of this, personalized tailored interventions for restriction and prevention of cancer progression and metastasis will improve patient survival. This review defines crucial biological steps of the metastatic cascade, such as cell dissemination, migration and invasion as well as the action of metastasis suppressors. Targeting these biological steps with tailored therapeutic strategies of intervention or even prevention of metastasis using a wide range of small molecules will be discussed.
转移是癌症最致命的特性，严重限制了许多肿瘤实体的成功治疗。临床需求是由这样一个事实所决定的，即所有已经发生或将要发生远处转移的癌症患者，其生存期都会缩短。因此，癌症治疗的最终目标是通过基于新型分子靶向的小分子疗法来限制实体癌的转移。人们极其渴望能够识别出具有高转移风险且同时作为转移关键驱动因素的癌症患者的生物标志物。针对这些关键分子的临床干预将在转移干预方面产生高效性。由此，针对癌症进展和转移的限制与预防进行个性化定制的干预将提高患者生存率。本综述定义了转移级联反应的关键生物学步骤，如细胞播散、迁移和侵袭以及转移抑制因子的作用。我们将讨论如何使用广泛的小分子，通过量身定制的干预甚至预防转移的治疗策略来靶向这些生物学步骤。
