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

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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1625-1631
Number of pages7
JournalNature Medicine
Volume19
Issue number12
DOIs
StatePublished - Dec 2013

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Tumors
Residual Neoplasm
Recurrence
Neoplasms
Phenotype
Screening
Innate Immunity
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence. / Kottke, Timothy; Boisgerault, Nicolas; Diaz, Rosa Maria; Donnelly, Oliver; Rommelfanger-Konkol, Diana; Pulido, Jose S; Thompson, Jill; Mukhopadhyay, Debabrata; Kaspar, Roger; Coffey, Matt; Pandha, Hardev; Melcher, Alan; Harrington, Kevin; Selby, Peter; Vile, Richard Geoffrey.

In: Nature Medicine, Vol. 19, No. 12, 12.2013, p. 1625-1631.

Research output: Contribution to journalArticle

Kottke, T, Boisgerault, N, Diaz, RM, Donnelly, O, Rommelfanger-Konkol, D, Pulido, JS, Thompson, J, Mukhopadhyay, D, Kaspar, R, Coffey, M, Pandha, H, Melcher, A, Harrington, K, Selby, P & Vile, RG 2013, 'Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence', Nature Medicine, vol. 19, no. 12, pp. 1625-1631. https://doi.org/10.1038/nm.3397
Kottke T, Boisgerault N, Diaz RM, Donnelly O, Rommelfanger-Konkol D, Pulido JS et al. Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence. Nature Medicine. 2013 Dec;19(12):1625-1631. https://doi.org/10.1038/nm.3397
Kottke, Timothy ; Boisgerault, Nicolas ; Diaz, Rosa Maria ; Donnelly, Oliver ; Rommelfanger-Konkol, Diana ; Pulido, Jose S ; Thompson, Jill ; Mukhopadhyay, Debabrata ; Kaspar, Roger ; Coffey, Matt ; Pandha, Hardev ; Melcher, Alan ; Harrington, Kevin ; Selby, Peter ; Vile, Richard Geoffrey. / Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence. In: Nature Medicine. 2013 ; Vol. 19, No. 12. pp. 1625-1631.
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