Novel therapeutic strategies to selectively kill cancer cells.

Tumor invasion, metastasis, and resistance to chemotherapeutic drugs or radiation are major obstacles for the successful treatment of cancer. To overcome some of these limitations, therapeutic strategies that increase the specificity and efficacy and reduce the toxicity of the anti-cancer drugs or toxins are being explored. Cancer cells overexpress specific protein antigens and carbohydrate structures that may function as cell surface receptors. These cancer cell specific markers can be exploited while designing new cancer therapies. Monoclonal antibodies that have been humanized to reduce immunogenicity and targeted to specific antigens on cancer cells, enzyme-monoclonal antibody/prodrug conjugates that will selectively kill the target cells following drug activation, and recombinant toxins are some of the novel classes of agents in development. 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 stimulus. These pore-forming cytolytic toxins can be rendered active by tumor-specific proteases, that are often overexpressed in cancer cells, thereby targeting the toxic effects. Such pore-forming or membrane-acting toxins may serve as novel cytolytic agents against solid tumors, which, to date, have proved to be more resistant to conventional toxins.