title: Characterization of surgical models of postoperative tumor recurrence for preclinical adjuvant therapy assessment.
abstract: OBJECTIVE
  Nearly 30% of cancer patients undergoing curative surgery succumb to distant recurrent disease. Despite large implications and known differences between primary and recurrent tumors, preclinical adjuvant therapy evaluation frequently occurs only in primary tumors and not recurrent tumors. We hypothesized that well characterized and reproducible models of postoperative systemic recurrences should be used for preclinical evaluation of adjuvant approaches.
  
  
  METHODS
  We examined traditional animal models of cancer surgery that generate systemic cancer recurrences. We also investigated models of systemic cancer recurrences that incorporate spontaneously metastatic cell lines and surgical resection. For each model, we critiqued feasibility, reproducibility and similarity to human recurrence biology. Using our novel model, we then tested the adjuvant use of a novel systemic inhibitor of TGF-β, 1D11.
  
  
  RESULTS
  Traditional surgical models are confounded by immunologic factors including concomitant immunity and perioperative immunosuppression. A superior preclinical model of postoperative systemic recurrences incorporates spontaneously metastatic cell lines and primary tumor excision. This approach is biologically relevant and readily feasible. Using this model, we discovered that "perioperative" TGF-β blockade has strong anti-tumor effects in the setting of advanced disease that would not be appreciated in primary tumor cell lines or other surgical models.
  
  
  CONCLUSIONS
  There are multiple immunologic effects that rendered previous models of postoperative cancer recurrences inadequate. Use of spontaneously metastatic cell lines followed by surgical resection eliminates these confounders, and best resembles the clinical scenario. This preclinical model provides more reliable preclinical information when evaluating new adjuvant therapies.
authors.forename: Jarrod D
authors.initials: JD
authors.lastname: Predina
authors.forename: Brendan
authors.initials: B
authors.lastname: Judy
authors.forename: Veena
authors.initials: V
authors.lastname: Kapoor
authors.forename: Aaron
authors.initials: A
authors.lastname: Blouin
authors.forename: Louis A
authors.initials: LA
authors.lastname: Aliperti
authors.forename: Daniel
authors.initials: D
authors.lastname: Levine
authors.forename: Olugbenga T
authors.initials: OT
authors.lastname: Okusanya
authors.forename: Jon
authors.initials: J
authors.lastname: Quatromoni
authors.forename: Zvi G
authors.initials: ZG
authors.lastname: Fridlender
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal