Cancer therapy by means of irreversible tumor blood flow stasis: Starvation tactics against solid tumors

Despite extensive research efforts, effective therapies for advanced cancers have not yet been established, and development of successful treatment strategies remains the most important task in the field of oncology. Three significant problems in conventional chemotherapy using cytotoxic drugs require attention: (i) choosing the most effective drug for individual patients, (ii) delivering a sufficient dose of drug to tumor, and (iii) minimizing severe side effects of anticancer drugs. Because the cancer cells are themselves the direct target of the drugs, these three problems cannot be avoided. We recently showed that AC7700 (currently AVE8062) a derivative of combretastatin A-4, achieved irreversible stasis of tumor blood flow (TBF), thereby causing necrosis of tumor tissue by halting the supply of nutrients. Such effects were unrelated to cancer type, in that they were found for various solid tumors. In this review, we summarize our research on AC7700 and tumor vessels and discuss how AC7700 causes stasis of TBF and why the blood flow does not resume. This technique of attacking tumor by means of blocking TBF largely avoids the three problems typically encountered in conventional cancer chemotherapy that were mentioned above. We propose that such starvation tactics constitute a new therapeutic approach to solid tumors, including refractory cancers which are resistant to conventional cytotoxic drugs and recurrent cancers that have acquired drug resistance.