Abstract
Pluripotent cells can be grown in clonogenic assays. The tumour stem-cell fraction,
which accounts for <0.4% of the total cells, and which is considered the most relevant
cell type in the development of metastases and recurrences, is able to divide and
to form colonies in a semisolid matrix (agar or methylcellulose). Major applications
of the tumour clonogenic assay (TCA) are chemosensitivity testing of tumours and xenografts,
and for assessments within drug discovery programmes. Of critical relevance for the
usefulness of the TCA is whether it can predict sensitivity or resistance towards
clinically used agents. When we compared the response of human tumours established
as xenografts in nude mice in the TCA in vitro to that of the clinical response, 62% of the comparisons for drug sensitivity, and
92% of the comparisons for drug resistance were correct. The same percentage of true/false
observations was found when tumours were tested after serial passage in nude mice
in the TCA in vitro and their response compared to in vivo activity in corresponding xenografts (60% and 90%, respectively). The highest correct
predictive values were, however, found when the clinical response of tumours was compared
to their explants established in the nude mouse and treated in vivo. Of 80 comparisons performed, we observed a correct prediction for tumour resistance
in 97% and for tumour sensitivity in 90%. In our opinion, the TCA with established
human tumour xenografts has an important role in current drug discovery strategies.
We therefore included the TCA as secondary assay in our approach to anticancer drug
discovery and found that a number of novel agents were active; these are now in advanced
preclinical development or clinical trials. Thus, the tumour clonogenic assay has
proven predictive value in the chemosensitivity testing of standard and experimental
anticancer drugs.
Keywords
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Article info
Publication history
Accepted:
January 26,
2004
Received in revised form:
January 19,
2004
Received:
December 23,
2003
Identification
Copyright
© 2004 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
