Teicher Beverly A
Genzyme Corporation, Framingham, Massachusetts 01701-9322, USA.
Clin Cancer Res. 2008 Mar 15;14(6):1610-7. doi: 10.1158/1078-0432.CCR-07-2249.
The plasticity and instability of the cancer genome is impressive and is characterized by gene amplifications and deletions, rearrangements, and many silent and active mutations. Although targeted therapeutics have had effect in some diseases, there remains a large role for new cytotoxic agents that have the potential to be broadly active across multiple cancers. Platinum-based regimens are the basis for treatment of several common tumors. Satraplatin and picoplatin are newer platinum complexes that form bulkier lesions in DNA than their forerunners. Microtubules are a key target for anticancer agents. Vinca alkaloid and similar compounds fragment these critical structures, whereas taxanes stabilize them. Vinflunine is a new fluorinated Vinca alkaloid derivative with vascular disrupting effects, as well as antitumor effects. Epothilones are a new class of microtubule stabilizers. Mitosis has been targeted directly and indirectly by many anticancer agents. The aurora kinases are new targets in this class. Inhibitors of aurora kinases are likely to be cytotoxic. Finally, protein regulation is essential for cellular integrity. With the approval of bortezomib (Velcade, PS-341), the proteosome, a master protein regulator, has been validated as an anticancer target. The five articles in this issue of CCR Focus present the current status of these next generation cytotoxic agents.
癌症基因组的可塑性和不稳定性令人瞩目，其特征包括基因扩增与缺失、重排以及众多沉默和活性突变。尽管靶向治疗在某些疾病中已见成效，但新型细胞毒性药物仍发挥着重要作用，这类药物有可能对多种癌症具有广泛的活性。铂类方案是几种常见肿瘤治疗的基础。沙铂和匹铂是新型铂配合物，与它们的前身相比，能在DNA中形成更大的损伤。微管是抗癌药物的关键靶点。长春花生物碱及类似化合物会破坏这些关键结构，而紫杉烷则使其稳定。长春氟宁是一种新型氟化长春花生物碱衍生物，具有血管破坏作用以及抗肿瘤作用。埃博霉素是一类新型微管稳定剂。许多抗癌药物直接或间接靶向有丝分裂。极光激酶是这一类别的新靶点。极光激酶抑制剂可能具有细胞毒性。最后，蛋白质调控对于细胞完整性至关重要。随着硼替佐米（万珂，PS - 341）获批，蛋白酶体作为主要的蛋白质调节因子，已被确认为抗癌靶点。本期《临床肿瘤研究聚焦》中的五篇文章介绍了这些新一代细胞毒性药物的现状。
