Metastasis is the main cause of anti-cancer therapy failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses relies on the development of efficient therapeutic strategies specifically directed against key targets in the metastatic process. Traditional chemotherapy with classical alkylating agents, microtubule inhibitors, and antimetabolites has demonstrated its limited efficacy against metastatic cells due to their capacity to select chemo-resistant cell populations that undergo epithelial-to-mesenchymal transition (EMT), thus promoting the colonization of distant sites that, in turn, sustain the initial metastatic process. This scenario has prompted efforts aimed at discovering a wide variety of small molecules and biologics as potential anti-metastatic drugs directed against more specific targets known to be involved in the various stages of metastasis. In this short review, we give an overview of the most recent advances related to important families of antimetastatic small molecules: intracellular tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors, KRAS inhibitors, and integrin antagonists. Although the majority of these small molecules are not yet approved and not available in the drug market, any information related to their stage of development could represent a precious and valuable tool to identify new targets in the endless fight against metastasis.
转移是抗癌治疗失败的主要原因，导致患者预后不良。通过将癌症转变为具有周期性但可控复发的慢性疾病来提高癌症患者预期寿命的真正挑战，在于开发针对转移过程中关键靶点的有效治疗策略。传统化疗药物（如经典烷化剂、微管蛋白抑制剂和抗代谢药物）因其易筛选出发生上皮-间质转化的化疗耐药细胞群，从而促进远端部位定植并维持初始转移进程，已证明其对转移细胞的疗效有限。这一现状促使人们致力于发现多种小分子药物和生物制剂作为潜在抗转移药物，这些药物针对已知参与转移各阶段的更特异性靶点。本短篇综述概述了抗转移小分子重要家族的最新进展：细胞内酪氨酸激酶抑制剂、细胞周期蛋白依赖性激酶抑制剂、KRAS抑制剂和整合素拮抗剂。尽管这些小分子药物大多尚未获批上市，但与其研发阶段相关的任何信息都可能成为在抗击转移的持久战中识别新靶点的宝贵工具。
Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams
肿瘤(癌症)患者之家