Authors: Jarrod D. Predina, Brendan Judy, Zvi G. Fridlender, Louis A. Aliperti, Brian Madajewski, Veena Kapoor, Guanjun Cheng, Jon Quatromoni, Olugbenga Okusanya and Sunil Singhal

Jarrod D. Predina

Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Brendan Judy

Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Zvi G. Fridlender

Institute of Pulmonary Medicine; Hadassah-Hebrew University Medical Center; Jerusalem, Israel

Louis A. Aliperti

Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Brian Madajewski

Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Veena Kapoor

Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Guanjun Cheng

Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Jon Quatromoni

Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Olugbenga Okusanya

Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Sunil Singhal

Corresponding author: sunil.singhal@uphs.upenn.edu
Thoracic Surgery Research Laboratory; Department of Surgery; University of Pennsylvania School of Medicine; Philadelphia, PA USA

Abstract:
Up to 30% of cancer patients undergoing curative surgery develop local recurrences due to positive margins. Patients typically receive adjuvant chemotherapy, immunotherapy and/or radiation to prevent such relapses. Interestingly, evidence supporting these therapies is traditionally derived in animal models of primary tumors, thus failing to consider surgically induced tumor microenvironment changes that may influence adjuvant therapy efficacy. To address this consideration, we characterized a murine model of local cancer recurrence. This model was reproducible and generated a postoperative inflammatory tumor microenvironment that resembles those observed following human cancer surgery. To further validate this model, antagonists of two pro-inflammatory mediators, TGFβ and COX-2, were tested and found to be effective in decreasing the growth of recurrent tumors. We appreciated that preoperative TGFβ inhibition led to wound dehiscence, while postoperative initiation of COX-2 inhibition resulted in a loss of efficacy. In summary, although not an exact replica of all human cancer surgeries, our proposed local recurrence approach provides a biologically relevant and reliable model useful for preclinical evaluation of novel adjuvant therapies. The use of this model yields results that may be overlooked using traditional preclinical cancer models that fail to incorporate a surgical component.

Received: January 4, 2012; Accepted: April 29, 2012; Published Online: May 23, 2012

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