Anti-cancer chemotherapy typically involves administration of maximum tolerated doses of one or more cytotoxic agents which show limited selectivity for tumours. While this strategy can be effective and has been the mainstay of chemotherapy for many years, patients often experience debilitating side-effects which greatly impact their quality of life. We’ve been investigating ways of achieving tumour selective combination therapy through linkage of two anti-tumour agents with differing modes of action (i.e. angiogenesis inhibitor and cytotoxin) into a single (mutual) prodrug that is selectively cleaved to reveal the active drugs only within the hypoxic regions of solid tumours. Progress towards the synthesis and proof-of-concept studies with prototype molecules will be presented, along with novel anti-angiogenic scaffolds that were discovered along the way.
