Bertino J R, Li W W, Lin J, Trippett T, Goker E, Schweitzer B, Banerjee D
Sloan-Kettering Institute for Cancer Research, Department of Medicine, Memorial Hospital, New York, NY 10021.
Mt Sinai J Med. 1992 Oct;59(5):391-5.
This brief review should serve to indicate that it is possible to assess tumor sensitivity to antifolates using fresh human tissue in short-term culture. The assays described differ from general assays of tumor sensitivity, such as the clonogenic assay or assays that measure 3H-thymidine incorporation as an indicator of cell viability (32-34), in that the effect of a drug on a human specific target (dihydrofolate reductase) is measured. These specific assays also may prove to be extremely useful in the detection of acquired drug resistance and for new analog drug development. In a general sense, this type of assay may eventually also be useful for guiding and selecting treatment for individual patients with other drugs with known mechanisms of action. Knowledge of the basis of tumor resistance is essential to develop new approaches to treatment, such as the use of other folate analogs that may still be effective, and to devise ways in which to selectively inhibit tumor cell growth using new analogs (trimetrexate) and leucovorin.
本简要综述旨在表明，利用短期培养的新鲜人体组织评估肿瘤对抗叶酸药物的敏感性是可行的。所描述的检测方法与一般的肿瘤敏感性检测方法不同，如克隆形成检测或测量3H-胸腺嘧啶核苷掺入作为细胞活力指标的检测方法（32 - 34），因为它测量的是药物对人类特定靶点（二氢叶酸还原酶）的作用。这些特异性检测方法在检测获得性耐药性和开发新的类似药物方面也可能被证明极为有用。一般来说，这种类型的检测最终可能也有助于指导和选择针对其他具有已知作用机制药物的个体患者的治疗方案。了解肿瘤耐药的基础对于开发新的治疗方法至关重要，例如使用可能仍然有效的其他叶酸类似物，以及设计使用新的类似物（三甲曲沙）和亚叶酸钙选择性抑制肿瘤细胞生长的方法。
