NOVEL THERAPEUTIC STRATEGIES TO SELECTIVELY KILL CANCER-CELLS

Tumor invasion, metastasis, and resistance to chemotherapeutic drugs o r radiation are major obstacles for the successful treatment of cancer . To overcome some of these limitations, therapeutic strategies that i ncrease the specificity and efficacy and reduce the toxicity of the an ti-cancer drugs or toxins are being explored. Cancer cells overexpress specific protein antigens and carbohydrate structures that may functi on as cell surface receptors. These cancer cell specific markers can b e exploited while designing new cancer therapies. Monoclonal antibodie s that have been humanized to reduce immunogenicity and targeted to sp ecific antigens on cancer cells, enzyme-monoclonal antibody/prodrug co njugates that will selectively kill the cells following drug activatio n, and recombinant toxins are some of the novel classes of agents in d evelopment. Another novel approach being investigated to treat cancers is the use of inactive pore-forming toxins with built-in biological ' 'triggers'' that will activate the toxin, following a biological stimu lus. These pore-forming cytolytic toxins can be rendered active by tum or-specific proteases, that are often overexpressed in cancer cells, t hereby targeting the toxic effects. Such pore-forming or membrane-acti ng toxins may serve as novel cytolytic agents against solid tumors, wh ich, to date, have proved to be more resistant to conventional toxins. (C) 1998 Elsevier Science Inc.