Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12

AUTHORS

Timothy Kottke, Nicolas Boisgerault, Rosa Maria Diaz, Oliver Donnelly, Diana Rommelfanger-Konkol, Jose Pulido, Jill Thompson, Debabrata Mukhopadhyay, Roger Kaspar, Matt Coffey, Hardev Pandha, Alan Melcher, Kevin Harrington, Peter Selby, Richard Vile

ABSTRACT

Tumor recurrence represents a major clinical challenge. Our data show that emergent recurrent tumors acquire a phenotype radically different from that of their originating primary tumors. This phenotype allows them to evade a host-derived innate immune response elicited by the progression from minimal residual disease (MRD) to actively growing recurrence. Screening for this innate response predicted accurately in which mice recurrence would occur. Premature induction of recurrence resensitized MRD to the primary therapy, suggesting a possible paradigm shift for clinical treatment of dormant disease in which the current expectant approach is replaced with active attempts to uncover MRD before evolution of the escape phenotype is complete. By combining screening with second-line treatments targeting innate insensitivity, up to 100% of mice that would have otherwise relapsed were cured. These data may open new avenues for early detection and appropriately timed, highly targeted treatment of tumor recurrence irrespective of tumor type or frontline treatment. More... »

PAGES

1625-1631

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nm.3397

    DOI

    http://dx.doi.org/10.1038/nm.3397

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24240185


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