Kurbacher Christian M, Cree Ian A
Department of Gynecology and Obstertrics, University of Cologne, Cologne, Germany.
Methods Mol Med. 2005;110:101-20. doi: 10.1385/1-59259-869-2:101.
During the last two decades, novel nonclonogenic methods for pretherapeutic chemosensitivity testing have been developed that are likely to overcome major technical limitations of older assays such as low evaluability rates, low degree of standardization and reproducibility, lack of technical robustness, and poor methodological efficacy. Among these, the microplate adenosine triphosphate (ATP)-based tumor chemosensitivity assay (ATP-TCA) has gained particular merits for ex vivo chemosensitivity testing of native nonhematological tumors including cancers of the breast, ovary, gastrointestinal tract, cervix and corpus uteri, and lung; malignant melanomas; gliomas; sarcomas; and mesotheliomas. For this indication, the ATP-TCA can now be considered the best documented and validated technology. This assay, which is now commercially available, provides a highly reproducible, easy-to-handle kit technique; low technical failure rates; and a high methodological efficacy requiring only 1 x 106 tumor cells to test four to six different drugs or combinations. In ovarian and breast carcinomas, the predictive accuracy is > 90%, with a positive predictive value of 85-90% and a negative predictive value near 100%, respectively. In primary ovarian cancers, the ATP-TCA has been found to accurately predict both clinical response and survival. In two prospective clinical trials in patients with heavily pretreated ovarian cancer, chemotherapy individually selected by the ATP-TCA has been found to triple the response rates and nearly double the survival compared to empirically chosen regimens. Consequently, this assay, which is now under phase III evaluation, has successfully been used in new agent development to screen for novel chemotherapy regimens for the treatment of patients with breast and ovarian carcinoma and melanoma, respectively. This chapter highlights the recent preclinical and clinical experience with this promising technology and gives a detailed description of all the technical aspects of the ATP-TCA.
在过去二十年中，已开发出新型非克隆生成方法用于治疗前化疗敏感性测试，这些方法可能克服了旧有检测方法的主要技术局限性，如评估率低、标准化和可重复性程度低、缺乏技术稳健性以及方法学效能差等问题。其中，基于微孔板三磷酸腺苷（ATP）的肿瘤化疗敏感性检测（ATP-TCA）在对包括乳腺癌、卵巢癌、胃肠道癌、宫颈癌和子宫体癌以及肺癌等天然非血液系统肿瘤；恶性黑色素瘤；神经胶质瘤；肉瘤；以及间皮瘤进行体外化疗敏感性检测方面具有特别的优势。对于这一适应症，ATP-TCA现在可被视为记录最完善且经过验证的技术。该检测方法现已商业化，提供了一种高度可重复、易于操作的试剂盒技术；技术失败率低；并且方法学效能高，仅需1×10⁶个肿瘤细胞即可测试四至六种不同药物或组合。在卵巢癌和乳腺癌中，预测准确率>90%，阳性预测值分别为85 - 90%，阴性预测值接近100%。在原发性卵巢癌中，已发现ATP-TCA能够准确预测临床反应和生存期。在两项针对经过大量预处理的卵巢癌患者的前瞻性临床试验中，发现通过ATP-TCA单独选择的化疗方案与经验性选择的方案相比，反应率提高了两倍，生存期几乎延长了一倍。因此，这种目前正在进行III期评估的检测方法已成功用于新药研发，分别筛选用于治疗乳腺癌、卵巢癌和黑色素瘤患者的新型化疗方案。本章重点介绍了这项有前景的技术最近的临床前和临床经验，并详细描述了ATP-TCA的所有技术方面。
