Cree I A, Kurbacher C M
Department of Pathology, Institute of Ophthalmology, University College London, UK.
Anticancer Drugs. 1997 Jul;8(6):541-8. doi: 10.1097/00001813-199707000-00001.
The burgeoning understanding of the molecular basis of carcinogenesis and tumor drug resistance is matched by an appreciation of the complexity of individual tumors. This complexity underlies the heterogeneity of response to treatment and is a major barrier to improving the outcome of solid tumor chemotherapy. While individualization of chemotherapy is theoretically attractive, past attempts to provide such information have produced many papers and little progress. However, the disparate molecular make-up of tumors of the same clinicopathologic type suggests that there may be no alternative and recent progress suggests that individualization of cancer therapy could have considerable benefits. In this review, we consider the alternative methods which might be employed and the requirements which need to be met before they are introduced. It will be some time before molecular analysis can predict chemosensitivity, although this may prove feasible for more specific agents than those currently in use. However, newly developed cellular chemosensitivity assays such as the ATP-tumor chemosensitivity assay allied to selected molecular measurement may already have the potential to select optimal therapy for patients. We need to develop a diverse series of acceptable and biologically logical regimens for each of the common tumor types, all of which can be tested in vitro.
对癌症发生和肿瘤耐药性分子基础的迅速了解,与对单个肿瘤复杂性的认识相匹配。这种复杂性是治疗反应异质性的基础,也是改善实体瘤化疗效果的主要障碍。虽然化疗个体化在理论上很有吸引力,但过去提供此类信息的尝试产生了许多论文,却进展甚微。然而,相同临床病理类型肿瘤的不同分子组成表明,可能别无选择,而最近的进展表明癌症治疗个体化可能会带来相当大的益处。在这篇综述中,我们考虑了可能采用的替代方法以及在引入这些方法之前需要满足的要求。在分子分析能够预测化疗敏感性之前还需要一段时间,尽管对于比目前使用的药物更具特异性的药物来说,这可能证明是可行的。然而,新开发的细胞化疗敏感性检测方法,如与选定分子测量相关联的ATP肿瘤化疗敏感性检测,可能已经有潜力为患者选择最佳治疗方案。我们需要为每种常见肿瘤类型制定一系列多样的、可接受的且符合生物学逻辑的治疗方案,所有这些方案都可以在体外进行测试。