Abstract
Tumor biomarkers provide a quantitative tool for following tumor progression and response to therapy. However, investigations of clinically useful tumor biomarkers are time-consuming, costly, and limited by patient and tumor heterogeneity. In addition, assessment of biomarkers as indicators of therapy response is confounded by the concomitant use of multiple therapeutic interventions. Herein we report our use of a clinically relevant orthotopic animal model of malignant pleural mesothelioma for investigating tumor biomarkers. Utilizing multi-modality imaging with correlative histopathology, we demonstrate the utility and accuracy of the mouse model in investigating tumor biomarkers – serum soluble mesothelin-related peptide (SMRP) and osteopontin (OPN). This model revealed percentage change in SMRP level to be an accurate biomarker of tumor progression and therapeutic response – a finding consistent with recent clinical studies. This in vivo platform demonstrates the advantages of a validated mouse model for the timely and cost-effective acceleration of human biomarker translational research.
Highlights
Serum or plasma tumor biomarkers provide reliable, measurable, and noninvasive indicators of cancer detection, disease progression, and therapy response
We demonstrated a strong correlation between bioluminescent flux and pleural tumor volume as determined by magnetic resonance imaging (MRI), the gold standard for tumor volume assessment [13] (r = 0.86, p,0.0001, adjusted for within mouse clustering; Fig. 1C and D)
We have described an in vivo platform to investigate serum tumor biomarkers by combining quantitative bioimaging with an orthotopic mouse model
Summary
Serum or plasma tumor biomarkers provide reliable, measurable, and noninvasive indicators of cancer detection, disease progression, and therapy response. The standard Response Evaluation Criteria in Solid Tumors (RECIST) used to assess therapy response in solid tumors is inadequate for MPM because of the limitation of one-dimensional measurement for change in pleural tumor burden [7]. FDG-PET (fludeoxyglucose positron emission tomography) scans have been shown to correlate with therapy response [8,9], this technique possesses shortcomings in interpretations including false-positive uptake in inflamed tissues. This highlights the need for biomarkers that can be utilized to provide a quantitative measure of disease progression and therapy response. The use of biomarkers offers a potential investigational tool to understand tumor biology and the efficacy of novel experimental therapies in pre-clinical animal models
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