Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University Medical Center Göttingen, 37077 Göttingen, Germany.
1] Institute of Molecular Oncology, Göttingen Center of Molecular Biosciences, Ernst Caspari Haus, University Medical Center Göttingen, 37077 Göttingen, Germany. [2] Department of Pathology, School of Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
Nat Rev Drug Discov. 2014 Mar;13(3):179-96. doi: 10.1038/nrd4201.
Traditional anticancer chemotherapeutics targeting DNA replication and cell division have severe side effects, but they have proved to be highly successful in treating some cancers. Drugs targeting signalling oncoproteins that have gained tumour-driving functions through mutations or overexpression were subsequently developed to increase specificity and thus reduce side effects, but have limitations such as the development of resistance. Now, a new wave of small-molecule anticancer agents is emerging, targeting complex multicomponent cellular machineries - including chromatin modifiers, heat shock protein chaperones and the proteasome - which thus interfere with those support systems that are more essential for cancer cells than for normal cells. Here, we provide our perspective on the advantages and limitations of agents that target tumour-supportive cellular machineries (other than those involving DNA replication), comparing them with agents that target signalling intermediates.
传统的针对 DNA 复制和细胞分裂的抗癌化疗药物具有严重的副作用，但它们已被证明在治疗某些癌症方面非常成功。随后开发了针对信号转导致癌蛋白的药物，这些蛋白通过突变或过度表达获得了肿瘤驱动功能，以提高特异性从而降低副作用，但存在耐药性发展等局限性。现在，出现了一波新的小分子抗癌药物，针对复杂的多成分细胞机制——包括染色质修饰剂、热休克蛋白伴侣和蛋白酶体——从而干扰那些对癌细胞比正常细胞更重要的支持系统。在这里，我们比较了针对信号转导中间产物的药物，提供了针对肿瘤支持性细胞机制（不包括涉及 DNA 复制的药物）的药物的优势和局限性的观点。
