Novel chemotherapeutic agents for the treatment of brain cancer

Brain cancer encompasses both primary and metastatic brain rumours and acco unts for over 120,000 new patients each year. Despite aggressive therapy, t he majority of patients with brain cancer have poor prognosis and have brie f survival intervals. Current chemotherapy drugs, used alone or in combinat ion, have minimal or only modest activity. Novel agents that have recently been applied to brain cancer include temozolomide, irinotecan and paclitaxe l. Temozolomide is a DNA alkylating agent, irinotecan inhibits DNA topoisom erase I and paclitaxel binds to microtubules and induces polymerisation. Ne oplastic angiogenesis and brain tumour invasion are also targets for therap eutic intervention with new agents such as thalidomide, suramin and marimas tat. All of these agents have demonstrated activity against brain cancer in vitro. Several of the drugs, in particular temozolomide, paclitaxel. and i rinotecan, have entered preliminary clinical trials and have demonstrated s ome efficacy. However, chemotherapy for primary brain tumours remains rathe r non-specific and mostly ineffective. The use of chemotherapy may be more effective against selected metastatic brain tumours. Continued basic resear ch is needed to further elucidate the genetic basis of transformation, tumo ur invasion and angiogenesis. It is hoped that this research will lead to n ew therapeutic targets for drug design and development In addition, new str ategies must be developed to overcome the problem of chemotherapy resistanc e.