In his 2011 American Society of Clinical Oncology (ASCO) Presidential Address, George Sledge (Indiana University Melvin, IN, USA) argued that cancers can be classified as 'stupid or smart' depending upon their muta-tional load. His thesis was that 'stupid' cancers have a single dominant mutation (e.g., CML and BCR-ABL) that can be effectively treated by targeting the key oncogenic protein with a single small molecule (e.g., imatinib/Gleevec?, Novartis Oncology, USA). Unfortunately, most patients suffer from 'smart' cancers, which are tumors with multiple 'driver' mutations, each one requiring its own specific inhibitor in order to potentially reverse the malignant phenotype. To improve outcomes for patients infested with smart cancers requires the development of 'smart therapeutics' — treatments that attack cancers in multiple ways. We argue that onco-lytic viruses (OVs) are smart therapeutics and, indeed, through genetic engineering can have their 'IQs' raised by several points.
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