Migrastatics-Anti-metastatic and Anti-invasion Drugs: Promises and Challenges.
Migrastatics-Anti-metastatic and Anti-invasion Drugs: Promises and Challenges.
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DOI：
10.1016/j.trecan.2017.04.008
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发表时间：
2017-06
期刊：
影响因子：
18.4
通讯作者：
Brábek J
中科院分区：
文献类型：
--
作者：
Gandalovičová A;Rosel D;Fernandes M;Veselý P;Heneberg P;Čermák V;Petruželka L;Kumar S;Sanz-Moreno V;Brábek J
在实体癌中，侵袭和转移占死亡率的90%以上。然而，在目前的抗癌疗法中，缺少特定类别的抗侵袭和抗转移药物。在这里，我们为干扰所有癌细胞侵袭和转移模式的药物创造了术语“migrationstatics”，以将这类药物与主要针对细胞增殖的常规细胞抑制药物区分开来。我们定义肌动蛋白聚合和收缩性作为抗偏头痛药物的靶点机制，并对候选抗偏头痛药物进行综述。这些抗转移药物的关键评估是必要的，因为它们可能会定义新的选择，用于治疗实体癌。局部浸润和转移，而不是克隆性增殖，是实体癌的主要特征。然而，对于实体癌的治疗，缺少特定类别的抗侵袭和抗转移药物。我们提出术语“抗迁移剂”用于干扰癌细胞侵袭的所有模式并因此干扰其转移能力的药物（例如，不仅抑制局部侵袭，而且抑制外渗和转移定植）。在实体癌中，耐药性是治疗失败的主要原因，并归因于靶点的突变。由于针对病因，虽然在学术上是可取的，可能是徒劳的，一个务实的和近期的选择是向下游移动，到细胞迁移和/或入侵的常见的介导因素，如肌动蛋白聚合和肌动球蛋白介导的收缩。
In solid cancers, invasion and metastasis account for more than 90% of mortality. However, in the current armory of anticancer therapies, a specific category of anti-invasion and antimetastatic drugs is missing. Here, we coin the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation. We define actin polymerization and contractility as target mechanisms for migrastatics, and review candidate migrastatic drugs. Critical assessment of these antimetastatic agents is warranted, because they may define new options for the treatment of solid cancers. Local invasion and metastasis, rather than clonal proliferation, are the dominant features of solid cancer. However, a specific category of anti-invasion and antimetastatic drugs is missing for treatment of solid cancer We propose the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasiveness and, consequently, with their ability to metastasize (e.g., inhibiting not only local invasion, but also extravasation and metastatic colonization). In solid cancer, drug resistance is the main cause of treatment failure, and is attributed to mutations of the target. Since targeting the cause, although academically desirable, may be futile, a pragmatic and near-term option is to move downstream, to common denominators of cell migration and/or invasion, such as actin polymerization and actomyosin-mediated contractility.