Sensitive/resistant tumour

Andrei, G., Snoeck, R., and De Clercq, E. (1994) Human brain tumour cell lines as cell substrate to demonstrate sensitivity/resistance of herpes simplex virus types 1 and 2 to nucleoside analogues. Antiviral Chem. Chemother. 5, 263-270. 

Bianco R, Garofalo S, Rosa R, Damiano V, Gelardi T, Daniele G Marciano R, Ciardiello F, Tortora G. (2008) Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs. Br J Cancer 98 923-930. 

Hybrid crosses were bred from a highly sensitive strain SWR/J mice and AKR/J mice highly resistant to 1,2-dimethylhydrazine carcinogenesis. 1,2-Dimethylhydrazine was injected subcutaneously at a dose of 20 mg/kg bw weekly with a total of 10 injections. Mice were killed 27 weeks after the first injection of 1,2-dimethylhydrazine. The colon tumour incidence in the hybrids and backcrosses is given in Table 15. The interpretation of results by the authors was that susceptibility to 1,2-dimethylhydrazine-induced tumorigenesis is not inherited as a dominant trait and that the kinetic properties of the epithelial cells are not linked to 1,2-dimethylhydrazine susceptibility (Deschner et al, 1988). 

Cositecan (Karenitecin , BNP 1350) 54 (BioNumerik and ASKA Pharmaceutical) is currently being evaluated in a Phase III trial for the treatment of patients with advanced ovarian cancer who have become resistant to platinum and taxane drugs.110 Cositecan 54,111 114 which is also being evaluated against solid tumours in a Phase I trial, is an orally bioavailable, lipophilic 7-[2-(tri-methylsilyl)ethyl] derivative of camptothecin 55 which is less sensitive to both common and camptothecin-specific resistance mechanisms. Camptothecin 55 was first isolated in 1958 from Camptotheca acuminata (Nyssaceae) and its structure was reported in 1966.115 117 Camptothecin 55 was later shown to be a topoisomerase I inhibitor two camptothecin derivatives, topotecan and iri-notecan, are approved for chemotherapy use. 

Resistance can be due to selection of cells already present in the tumour and which survive alkylation, or a result of enzyme induction in non-lethally alkylated cells. If excision repair is the major cause of resistance, then sensitivity might be restored by interfering with the repair process, and some progress has already been made in this direction74). 

TABLE 2. Cytotoxicity (IC50 pM) of Au(III) complexes towards the ovarian tumour cell line panel. Cisplatin is shown for comparison. The numbers in parentheses represent resistance factors (IC50 of resistant cell line IC50 sensitive cell line) ... 

These observations were further supported by the pharmacological studies. For example, in the ovarian cell line panel the acetate was equally active against a cisplatin-resistant cell line, CH1R, as against its cisplatin-sensitive counterpart, CHI. The mechanism of resistance to cisplatin in this cell line is repair of cisplatin-induced DNA damage. Also, [Au(OAc)2(damp)] had little activity against the ADJ/PC6 murine tumour, which is known to be particularly sensitive to compounds which cross-link DNA, such as cisplatin69. 

Somfai-Relle, S., Suzukake, K., Vistica, B. P., and Vistica, D. T., Reduction in cellular glutathione by buthionine sulphoximine and sensitization of murine tumour cells resistant to L-phenylalanine mustard. Biochem. Pharmacol. 33, 485 (1984). 

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