Dy Grace K, Adjei Alex A
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Cancer. 2008 Oct 1;113(7 Suppl):1857-87. doi: 10.1002/cncr.23651.
The 1940s marked the beginning of an era of important discoveries that contributed to modern concepts underlying the current practice of cancer chemotherapy, such as the log kill hypothesis reported by Skipper, the Norton-Simon hypothesis, and the Goldie-Coldman hypothesis. The early success of nitrogen mustards and antifolates in the treatment of hematologic malignancies paved the way for drug discovery platforms, which resulted in the generation of more drugs that nonetheless predominantly are genotoxic. The turn of the new millennium marked a new phase in the evolution of cancer chemotherapy. Scientific progress in the preceding 60 years elucidated the important ideas behind tumor microenvironment and 'targeted' therapy that had their inception in the late 19th century. Breakthroughs in molecular biology have paved the way for the development of novel agents that modulate the dysregulated molecular pathways implicated in carcinogenesis. The key approaches and evidence pertinent to the clinical development of these novel agents are presented in this review.
20世纪40年代标志着一个重要发现时代的开始，这些发现为现代癌症化疗实践的基础概念做出了贡献，比如斯基珀提出的对数杀伤假说、诺顿-西蒙假说以及戈尔迪-戈德曼假说。氮芥类药物和抗叶酸药物在治疗血液系统恶性肿瘤方面的早期成功为药物发现平台铺平了道路，这导致了更多药物的产生，不过这些药物主要是基因毒性药物。新千年的到来标志着癌症化疗发展进入了一个新阶段。此前60年的科学进展阐明了肿瘤微环境和“靶向”治疗背后的重要理念，这些理念始于19世纪末。分子生物学的突破为开发新型药物铺平了道路，这些药物可调节与致癌作用相关的失调分子途径。本综述介绍了与这些新型药物临床开发相关的关键方法和证据。
