Acquisition of platinum drug resistance and platinum cross resistance patterns in a panel of human ovarian carcinoma xenografts

Abstract

Summary In vivo models of acquired resistance to the platinum-based agents cisplatin (CDDP), carboplatin (CBDCA), iproplatin (CHIP) In addition to primary resistance, the acquisition of tumour resistance to the platinum-based drugs cisplatin and carboplatin often results in unsuccessful treatment outcome. This is particularly the case for advanced ovarian cancer, where despite initial response rates of the order of 50%, the majority of patients will ultimately succumb to their disease (Ozols, 1991). Although carboplatin is undoubtedly able to offer patients a more acceptable level of morbidity compared to cisplatin, the results of both randomised and cross-over studies indicate that the two agents are effective against essentially the same population of tumours (Gore et al., 1989;Mangioni et al., 1989;Eisenhauer et al., 1990;Advanced Ovarian Trialists Group, 1991). Therefore, there remains an unequivocal need to discover and develop additional drugs which possess activity against cisplatin/carboplatin-resistant tumours.

Platinum‐based anticancer agents: Innovative design strategies and biological perspectives

“…81,82 Other research groups have also reported the cytotoxic activity of DACH complexes in other cisplatin-resistant tumor cells. 83,84 Among the platinum derivatives bearing the DACH carrier ligand, compounds such as tetraplatin (9) reached the early clinical trial stage; however adverse therapeutic index and toxicity compromised its further development.…”

Multicellular Resistance: A New Paradigm to Explain Aspects of Acquired Drug Resistance of Solid Tumors

“…Variants were isolated which expressed resistance to the drug-antibody conjugate or to the unconjugated drug in nude mice, but their resistance properties were not expressed in monolayer tissue culture (Starling et al 1990). However, it is also clear that there are other examples in which human or mouse solid tumors made drug resistant in vivo will express their resistance properties in monolayer cell culture (Jones et al 1993).…”

BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma

“…Interestingly, in the A2780 cell lines BCL-2 was undetectable in the parent and cisR lines, but in the A2780/ZD0473 R line the levels were significantly higher. Kelland et al (1992a, b) and Jones et al (1993). Levels of the BCL-2 family proteins in a panel of human ovarian carcinoma xenografts of varying responsivenesss to cisplatin are shown in Table 1.…”