期刊
CANCER BIOLOGY & THERAPY
卷 13, 期 9, 页码 745-755出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.20557
关键词
surgical model; tumor microenvironment; adjuvant therapy; immunotherapy; cancer recurrence; oncology
类别
资金
- American Medical Association
- National Institutes of Health [TL1RR024133, K12CA076931]
- Lavin Family Supporting Foundation
- Society of Surgical Oncology
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, TGF beta and COX-2, were tested and found to be effective in decreasing the growth of recurrent tumors. We appreciated that preoperative TGF beta 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.
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