In: Chemotherapy19 Nov 2014
In vitro Drug Sensitivity Testing
Selection of individualized chemotherapy based on in vitro drug sensitivity testing (DST) has been a goal of clinicians for more than 3 decades. Despite intense interest and research, and the development of multiple assay methods, this goal has remained theoretic for the most part. In applying such procedures, the following points must be carefully considered: How do you test?; What do you test?; How do you interpret and apply the data?; and (most important of all), What is its clinical relevance? While a detailed discussion of these points is beyond the scope of this report, certain aspects will be considered, in particular those that impact on lung cancer. website
A large number of assay end points have been utilized for DST. These include clonogenic assays, and those that measure cell proliferation and cell kill. Other assays are based on the measurement of early tumor cell damage, and include dye exclusion, enzyme assays, DNA replication, protein determinations, and the previously mentioned subrenal capsule assay. The multitude of techniques suggests that no single technique is satisfactory for all situations. Ever since its application for DST, the human tumor clonogenic assay has remained the gold standard for predictive tests. However, its general application has been hampered by many problems, both theoretic and practical. The major advantage of clonogenic methods is that clonogenic potential is limited to tumor cells, thus permitting testing of fresh tumor samples (which invariably are mixtures of tumor and non-tumor cells) to be tested. In our experience with fresh lung cancer specimens, relatively few positive samples yielded sufficient colonies for adequate testing. Subsequent technical improvements (including the use of tritiated thymidine end points and cloning in capillary tubes) have enhanced the clonogenic potential of many tumors, and have shortened the assay time.
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