ABSTRACT

While most earlier studies used a range of animal tumor model systems, there has now been more detailed examination of human tumors growing either as monolayers or in suspension, as multicellular spheroids, or in organotypic culture (reviewed in Chapter 12). These types of investigations still need extending and there is now the potential for evaluating not only a range of tumor cell lines of specific histologic types, but also those expressing a range of radiosensitivities or drug sensitivities. For example, Weichselbaum et have cultured human tumor cells from patients treated unsuccessfully with radiotherapy which proved radioresistant in vitro; Ozols and his colleagues3 have established a number of cell lines from both untreated and previously treated patients with ovarian cancer expressing differential sensitivities to adriamycin (ADR) and to cisplatin (CDDP); a range of resistant sublines, for e ~ a m p l e , ~ - ~ have been derived by exposure to certain drugs in vitro (see also sections in Chapters 2, 12, and 13). The point has also been made that there is not necessarily a direct correlation between radioresistance and drug re~istance.~.~.' In addition, we have shown that prior exposure to X-irradiation does not result in any systemic expression of radioresistan~e.~ The impact of combined treatments on these clearly defined radioresistant andtor drug resistant human tumor cell populations is an obvious area for future studies. These types of investigations can also be extended to human tumors in primary culture or the direct use of biopsy material, now that more successful in vitro growth conditions have been established. For example:

1. A novel cell culture system has been reported for the growth of ovarian tumors, which has facilitated evaluations of their CDDP sensitivities9

2. Differences in radiation sensitivity have been identified amongst cell populations isolated directly from human tumor surgical specimens"

3. Successful primary monolayer culturing of human tumor cells using cell-adhesive

matrix and supplemented medium have permitted drug and radiation sensitivity measurements1'

4. Peters et a1.,12 applying new techniques for setting up primary cultures from human biopsy or surgical specimens, have sought correlations between survival fractions at 2 Gy and radiotherapy response, for each particular tumor tested

Such work is obviously of importance and may also permit identification of any artefacts associated with the use of long-term cultured cells.