Abstract
2′,2′-Difluorodeoxycytidine (gemcitabine, dFdC) is a deoxycytidine (dCyd) analog with proven activity in solid tumors, including ovarian cancer, both in vitro and in vivo (1–3). In the cell dFdC is phosphorylated by deoxycytidine kinase (dCK) to its monophos-phate and subsequently to its triphosphate dFdCTP, which can be incorporated into DNA and RNA (4,5). In the DNA, exonuclease activity is unable to excise dFdCMP (5). Resistance to cytostatic agents commonly occurs during cancer treatment and is often associated with cross-resistance to other related and unrelated drugs. AG6000 is a variant of the human ovarian cancer cell line A2780, which was made resistant to dFdC. This resistance was associated with a total absence of dCK activity (8). In the initial characterization of this cell line we not only observed cross-resistance to related compounds such as other deoxynucleoside analogs, but also to unrelated compounds used in the treatment of ovarian cancer (8). Therefore we extended this study to a panel of other drugs used in and of potential interest for treatment of ovarian cancer. Several parameters known to be important in the metabolism of the different drugs were determined in A2780 and AG6000.
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Bergman, A.M., Pinedo, H.M., van Haperen, V.W.T.R., Veerman, G., Kuiper, C.M., Peters, G.J. (1998). Cross-Resistance of the Gemcitabine Resistant Human Ovarian Cancer Cell Line AG6000 to Standard and Investigational Drugs. In: Griesmacher, A., Müller, M.M., Chiba, P. (eds) Purine and Pyrimidine Metabolism in Man IX. Advances in Experimental Medicine and Biology, vol 431. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5381-6_113
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DOI: https://doi.org/10.1007/978-1-4615-5381-6_113
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