Department of Pharmacology, Vertex Pharmaceuticals, Inc., 130 Waverly Street, Cambridge, MA 02139, USA.
Curr Opin Pharmacol. 2010 Aug;10(4):385-90. doi: 10.1016/j.coph.2010.06.008. Epub 2010 Jul 12.
The poor success rate of discovering new, effective chemotherapeutics for oncology may reflect the failure of targeting treatments to the more aggressive, tumorigenic cells of the malignancy. Data have now emerged from several laboratories, examining both liquid and solid primary tumor tissues, that implicate cancer stem cells (CSCs) as the 'master-driver' cellular population for tumorigenicity. Moreover, these putative CSCs appear relatively resistant to existing chemotherapeutic and radiation therapy. Several different cellular pathways have been identified as likely mechanisms causal for the underlying insensitivity of the CSCs to conventional therapy. Progress has been made in the isolation and expansion of these CSCs for constructing conventional high-throughput phenotypic screening campaigns. However, challenges remain in designing optimal proof-of-concept trials for the clinical development of compounds targeting the elimination of CSCs.
肿瘤学中新的、有效的化疗药物发现成功率较低，这可能反映了靶向治疗未能针对恶性肿瘤中更具侵袭性、致瘤性的细胞。现在，来自几个实验室的数据表明，癌症干细胞 (CSC) 作为肿瘤发生的“主驱动”细胞群，液体和实体原发性肿瘤组织都涉及到这一点。此外，这些推测的 CSC 似乎对现有的化疗和放疗相对具有抗性。已经确定了几种不同的细胞途径作为 CSC 对常规治疗潜在不敏感的可能原因机制。在分离和扩增这些 CSC 以构建常规高通量表型筛选方面已经取得了进展。然而，在设计针对消除 CSC 的化合物的临床开发的最佳概念验证试验方面仍然存在挑战。
