Structurally Novel Platinum Antitumor Compounds
The more widespread and effective use of platinum complexes in cancer treatment is limited by inherent resistance (limited activity against many common human tumors) and the phenomenon of acquired drug resistance (reduced efficacy upon repeated treatment). The goals for new platinum complex synthesis thus remain activity in cisplatin-resistant cells and an altered spectrum of antitumor activity. Drug modifications may further allow for reduced toxicity and altered mode of delivery, such as by oral route or by liposome encapsulation. The complex biochemical factors which affect acquired resistance and cytotoxicity in both murine and human tumor cell lines include platinum uptake and efflux, enhanced repair of Pt-DNA lesions and increased levels of glutathione and/or metallothionein in resistant cells. Chemical modification directed to overcoming one or more of these factors can thus increase activity in cisplatin-resistant cells. Delineation of the molecular mechanisms of the various contributing factors to resistance can permit design of strategies to diminish or overcome completely the resistance. Clinical application of these studies could, in principle, produce a very useful adjunct to cisplatin treatment.
KeywordsAntitumor Activity Resistance Factor Human Tumor Cell Line Platinum Complex Platinum Atom
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