Bremer Edwin, van Dam Go, Kroesen Bart Jan, de Leij Lou, Helfrich Wijnand
Groningen University Institute for Drug Exploration (GUIDE), Department of Pathology and Laboratory Medicine, Section Medical Biology, Laboratory for Tumor Immunology, University Medical Center Groningen, University of Groningen, The Netherlands.
Trends Mol Med. 2006 Aug;12(8):382-93. doi: 10.1016/j.molmed.2006.06.002. Epub 2006 Jun 23.
Important breakthroughs in cancer therapy include clinical application of antibodies, such as Rituximab, and small inhibitory molecules, such as Iressa and Velcade. In addition, recent reports have indicated the therapeutic potential of physiological pro-apoptotic proteins such as TRAIL and galectin-1. Although unrelated at first glance, each strategy relies on the deliberate and selective induction of apoptosis in malignant cells. Importantly, therapy-resistance in cancer is frequently associated with de-regulation in the mechanisms that control apoptosis. However, cancer cells are often reliant on these molecular aberrations for survival. Therefore, selective induction of apoptosis in cancer cells but not normal cells seems feasible. Here, we review recent progress and prospects of selected novel anti-cancer approaches that specifically target and sensitize cancer cells to apoptosis.
癌症治疗的重要突破包括抗体(如利妥昔单抗)和小分子抑制剂(如易瑞沙和万珂)的临床应用。此外,最近的报告表明了诸如肿瘤坏死因子相关凋亡诱导配体(TRAIL)和半乳糖凝集素-1等生理性促凋亡蛋白的治疗潜力。尽管乍一看这些策略并无关联,但每种策略都依赖于在恶性细胞中刻意且选择性地诱导细胞凋亡。重要的是,癌症中的治疗抗性常常与控制细胞凋亡机制的失调相关。然而,癌细胞往往依赖这些分子异常来存活。因此,选择性地诱导癌细胞而非正常细胞凋亡似乎是可行的。在此,我们综述了一些选定的新型抗癌方法的最新进展和前景,这些方法专门针对癌细胞并使其对细胞凋亡敏感。