TY - JOUR
T1 - Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence
AU - Kottke, Timothy
AU - Boisgerault, Nicolas
AU - Diaz, Rosa Maria
AU - Donnelly, Oliver
AU - Rommelfanger-Konkol, Diana
AU - Pulido, Jose
AU - Thompson, Jill
AU - Mukhopadhyay, Debabrata
AU - Kaspar, Roger
AU - Coffey, Matt
AU - Pandha, Hardev
AU - Melcher, Alan
AU - Harrington, Kevin
AU - Selby, Peter
AU - Vile, Richard
N1 - Funding Information:
We thank T. Higgins for expert secretarial assistance and M. Behrens and K. Knutson for help with Her-2-neu mice. This work was supported by the Richard M. Schulze Family Foundation, the Mayo Foundation, Cancer Research UK, US National Institutes of Health grants R01 CA107082, R01CA130878 and R01 CA132734 and a grant from T. and J. Paul.
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
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U2 - 10.1038/nm.3397
DO - 10.1038/nm.3397
M3 - Article
AN - SCOPUS:84889885063
SN - 1078-8956
VL - 19
SP - 1625
EP - 1631
JO - Nature Medicine
JF - Nature Medicine
IS - 12
ER -