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“resistance is futile”

Gene Therapy volume 6, pages 1646–1647 (1999)Cite this article

The transfer of drug resistance genes to mammalian cells is appealing for two reasons. The first arises from the concept of dose intensification in cancer therapy. For many years it has been argued that higher proportions of cancer patients would be curable if they could tolerate higher doses of cytotoxic drugs. Such tolerance could be achieved, in principle, by transferring appropriate drug resistance genes to vulnerable organs, rendering them less susceptible to unwanted toxicities. Since bone marrow is one of the most chemosensitive tissues in the body, ex vivo incorporation of drug-resistance genes into marrow progenitor cells, followed by their transplantation into cancer patients, should increase the host’s tolerance of cytotoxic agents, thus promoting a higher cure rate.1,2,3

The second reason is the potential value of using drug resistance genes to expand populations of therapeutically important cells. If, for example, marrow progenitors were transduced with both a drug-resistance gene and a therapeutic gene, administration of even small doses of the relevant cytotoxic drug should selectively spare – and therefore selectively enrich – the population of transduced cells.4 This application has generated increasing interest among hematologists, who have come to realize that, without further selection, the numbers of cells transducible with current vectors are simply too small to produce clinically significant benefits.1,5,6

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  1. Center for Cell and Gene Therapy, Baylor College of Medicine, 6621 Fannin Street, MC 3-3320, Houston, 77030, Texas, USA

    M K Brenner

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Brenner, M. “resistance is futile”. Gene Ther 6, 1646–1647 (1999). https://doi.org/10.1038/sj.gt.3301045

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