{"entity":{"id":"paper-coffey-reovirus-ras-science-1998","kind":"paper","name":"Coffey 1998: reovirus grows in cells with an activated Ras pathway, which describes a great many cancers","aka":[],"tldr":"A common gut virus that does almost nothing in healthy adults turned out to need a switched-on growth pathway to replicate, and that switch is stuck on in a large share of human cancers.","summary":"Human reovirus requires an activated Ras signalling pathway to infect cultured cells. Coffey and colleagues tested whether that dependence could be used against tumours. A single intratumoural injection caused regression in 65 to 80 per cent of severe combined immunodeficient mice bearing tumours from v-erbB-transformed murine NIH 3T3 cells or human U87 glioblastoma cells. In immunocompetent C3H mice bearing tumours from ras-transformed C3H-10T1/2 cells, regression also occurred but needed a series of injections.\n\nThis is the second of the two classic selectivity arguments, alongside the interferon defect: a naturally occurring, essentially harmless virus whose replication requirement happens to be a hallmark of transformed cells. It became the basis of pelareorep, the reovirus product that has been in clinical trials for more than two decades.","asOf":"2026-09-25","links":[{"label":"Science 1998","url":"https://doi.org/10.1126/science.282.5392.1332"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9812900/"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1998,"doi":"10.1126/science.282.5392.1332","pmid":"9812900","authors":"Coffey MC, Strong JE, Forsyth PA, Lee PW","paperType":"basic","findings":["Human reovirus requires an activated Ras signalling pathway to infect cultured cells.","A single intratumoural injection caused tumour regression in 65 to 80 per cent of severe combined immunodeficient mice bearing v-erbB-transformed murine or human U87 glioblastoma tumours.","In immunocompetent C3H mice with ras-transformed tumours regression also occurred, but only after a series of injections rather than one."],"whatItMeans":"Selectivity does not have to be engineered. A wild virus can already prefer cancer cells if its replication depends on something the cancer has turned on. The difference between one injection in an immunodeficient mouse and a series in an immunocompetent one is the first clear signal in the literature that the host immune response both helps and hinders, which is still the central tension of the field.","caveats":["Ras pathway activation is common but is not measured before treatment in the reovirus trials, so the selectivity argument has never been tested as a biomarker in patients.","Rodent tumour models greatly overstate what intratumoural virus achieves in human tumours, which are larger, older and more fibrous.","Pelareorep, the product built on this work, has run for more than twenty years without a positive randomised phase 3 result."]},"route":"/key-papers/paper-coffey-reovirus-ras-science-1998/","neighbours":{"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}],"journal":[{"id":"science","kind":"journal","name":"Science","route":"/journals/science/"}]}}