Gascoigne Karen E, Taylor Stephen S
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
J Cell Sci. 2009 Aug 1;122(Pt 15):2579-85. doi: 10.1242/jcs.039719.
In 2007, over 12-million people were diagnosed with cancer. According to the American Cancer Society, at least one third of these individuals are not expected to survive the disease, making cancer the second most prevalent cause of death worldwide. Systemic chemotherapy forms the mainstay of cancer treatment, and agents that disrupt mitotic spindle assembly - so called ;anti-mitotics' - are commonly used to treat a wide variety of cancers. Traditional anti-mitotic agents include the microtubule toxins such as taxol, other taxanes and the vinca alkaloids, all of which have proven successful in the clinic. However, patient response remains highly unpredictable, and drug resistance is common. In addition, toxicity is a problem. To address these limitations, a new generation of anti-mitotic drugs is being developed. As the first wave of these new agents enters clinical trails, much hope rests on their outcome. Meanwhile, significant attention is being focused on trying to predict which tumour types are likely to respond. In this Commentary, we outline recent advances in our understanding of how cancer cells respond to anti-mitotic drugs, and discuss the relevance of these studies to their use in the clinic.
2007年,超过1200万人被诊断患有癌症。根据美国癌症协会的数据,预计这些患者中至少有三分之一无法从该疾病中存活下来,这使得癌症成为全球第二大常见死因。全身化疗是癌症治疗的主要手段,而破坏有丝分裂纺锤体组装的药物——即所谓的“抗有丝分裂药物”——通常用于治疗多种癌症。传统的抗有丝分裂药物包括微管毒素,如紫杉醇、其他紫杉烷类和长春花生物碱,所有这些药物在临床上都已证明是成功的。然而,患者的反应仍然高度不可预测,而且耐药性很常见。此外,毒性也是一个问题。为了解决这些局限性,新一代抗有丝分裂药物正在研发中。随着这些新药的首批药物进入临床试验,人们对它们的结果寄予厚望。与此同时,大量注意力集中在试图预测哪些肿瘤类型可能会有反应。在这篇评论中,我们概述了我们对癌细胞如何对抗有丝分裂药物作出反应的理解方面的最新进展,并讨论了这些研究与它们在临床应用中的相关性。