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dc.contributor.authorVile, RG
dc.contributor.authorMelcher, A
dc.contributor.authorPandha, H
dc.contributor.authorHarrington, KJ
dc.contributor.authorPulido, JS
dc.date.accessioned2021-03-26T12:16:17Z
dc.date.available2021-03-26T12:16:17Z
dc.date.issued2021-02-08
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2021
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4451
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-20-1888
dc.description.abstractThe apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) family protects against infection by degrading incoming viral genomes through cytosine deamination. Here, we review how the potential to unleash these potent DNA mutagens comes at a price as APOBEC DNA mutagenesis can contribute to development of multiple types of cancer. In addition, since viral infection induces its expression, APOBEC is seen as the enemy of oncolytic virotherapy through mutation of the viral genome and by generating virotherapy-resistant tumors. Therefore, overall APOBEC in cancer has received a very poor press. However, we also speculate how there may be silver linings to the storm clouds (kataegis) associated with APOBEC activity. Thus, although mutagenic genomic chaos promotes emergence of ever more aggressive sub-clones, it also provides significant opportunity for cytotoxic and immune therapies. In particular, the superpower of cancer immunotherapy derives in part from mutation, wherein generation of tumor neoantigens - neoantigenesis - exposes tumor cells to functional T cell repertoires, and susceptibility to immune checkpoint blockade. Moreover, APOBECs may be able to induce supra-threshold levels of cellular mutation leading to mitotic catastrophe and direct tumor cell killing. Finally, we discuss the possibility that linking predictable APOBEC-induced mutation with escape from specific front line therapies could identify mutated molecules/pathways that can be targeted with small molecules and/or immunotherapies in a Trap and Ambush strategy. Together, these considerations lead to the counter-intuitive hypothesis that, instead of attempting to expunge and excoriate APOBEC activity in cancer therapy, it might be exploited - and even, counterintuitively, encouraged.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleAPOBEC and cancer viroimmunotherapy: Thinking the Unthinkable.
dc.typeJournal Article
dcterms.dateAccepted2021-01-19
rioxxterms.versionAM
rioxxterms.versionofrecord10.1158/1078-0432.ccr-20-1888
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2021-02-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.publication-statusPublished
pubs.embargo.termsNot known
icr.researchteamTargeted Therapy
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorHarrington, Kevinen


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