Peripheral blood monocytes as potential predictive biomarkers and therapeutic targets in colorectal cancer

• Applicant: Dr. Alexander Hamm
• Subject Area: General and Visceral Surgery
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 194490836

Colorectal cancer (CRC) is the third most common cancer and the fourth cause of cancer-related deaths worldwide. Given the strong dependence of disease prognosis on early detection, there is an urgent need to define key carcinogenesis-associated biomarkers. These could be used for early diagnosis and monitoring of disease progression in a non-invasive way. Peripheral blood is an easily accessible tissue and therefore suitable for screening of disease biomarkers. Among the cells circulating in peripheral blood, monocytes can be a promising target as they represent a source of macrophages and dendritic cells, contributing to tumor growth, metastasis and angiogenesis as well as anti-tumor immune response. The contribution of tumor-associated macrophages to the progression of the disease is controversial as high numbers of infiltrating tumor associated macrophages have been associated with both tumor growth and improved disease-free survival, suggesting distinct subpopulations with dual functional polarization. However, whether the genetic signature of monocytes can be used to predict the progression of the disease and the risk to develop distant metastasis is not known yet. The current proposal will (1) Identify predictive biomarkers by gene profiling of PBM from CRC patients,(2) Evaluate the expression of the PBM predictive biomarkers during early stages of tumor development and tumor progression in mouse models,(3) Evaluate the biological function of the PBM-associated genes in vitro,(4) Validate the function and therapeutic potential of the PBM-associated genes in CRC development and malignancy and evaluate the therapeutic potential of PBM in CRC.Using complementary experiments and techniques proposed herein, we will unveil highly valuable and much needed insights into colorectal cancer biology and possibly deliver novel scientific foundation for innovative diagnosis and therapy of colorectal cancer.

• DFG Programme: Research Fellowships
• International Connection: Belgium
• Host: Professor Massimiliano Mazzone, Ph.D.