null Pnina Brodt, PhD
cancer metastasis • tumor microenvironment • inflammation • colon cancer • breast cancer
My research focuses on biological and clinical aspects of cancer metastasis with emphasis on the process of liver metastasis. Cancer metastasis to vital organs such as the liver is the main cause of cancer-related death. Our aim is to identify therapeutic targets and develop novel anti-cancer agents for the prevention or treatment of metastases. We want to understand the pro-metastatic microenvironment of the liver. This project aims to elucidate the role of the microenvironment in controlling the growth of disseminated cancer cells in the liver. To this end, we are using genetically modified mouse models to dissect the contribution of specific immune cells and soluble factors to the promotion of cancer cell growth in the liver. We also want to develop an IGF Trap as an anti-cancer drug. Based on our findings that the IGF axis plays a critical role in the progression of liver metastasis, we have developed a soluble IGF-TRAP with potent tumor-inhibitory properties in vivo, in different tumor types. We are currently improving the structure and treatment protocols, in an effort to optimize this agent for clinical use.
Wang N, Fallavollita L, Nguyen L, Burnier J, Rafei M, Galipeau J, Yakar S, Brodt P. Autologous bone marrow stromal cells genetically engineered to secrete an igf-I receptor decoy prevent the growth of liver metastases. Mol Ther. 2009 Jul;17(7):1241-9. doi: 10.1038/mt.2009.82. Epub 2009 Apr 14. PMID: 19367255.
Burnier JV, Wang N, Michel RP, Hassanain M, Li S, Lu Y, Metrakos P, Antecka E, Burnier MN, Ponton A, Gallinger S, Brodt P. Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis. Oncogene. 2011 Sep 1;30(35):3766-83. doi: 10.1038/onc.2011.89. Epub 2011 Apr 11. PMID: 21478904.
Li S, Wang N, Brodt P. Metastatic cells can escape the proapoptotic effects of TNF-α through increased autocrine IL-6/STAT3 signaling. Cancer Res. 2012 Feb 15;72(4):865-75. doi: 10.1158/0008-5472.CAN-11-1357. Epub 2011 Dec 22. PMID: 22194466.
Van den Eynden GG, Majeed AW, Illemann M, Vermeulen PB, Bird NC, Høyer-Hansen G, Eefsen RL, Reynolds AR, Brodt P. The multifaceted role of the microenvironment in liver metastasis: biology and clinical implications. Cancer Res. 2013 Apr 1;73(7):2031-43. doi: 10.1158/0008-5472.CAN-12-3931. Epub 2013 Mar 27. PMID: 23536564.
Wang N, Rayes RF, Elahi SM, Lu Y, Hancock MA, Massie B, Rowe GE, Aomari H, Hossain S, Durocher Y, Pinard M, Tabariès S, Siegel PM, Brodt P. The IGF-Trap: Novel Inhibitor of Carcinoma Growth and Metastasis. Mol Cancer Ther. 2015 Apr;14(4):982-93. doi: 10.1158/1535-7163.MCT-14-0751. Epub 2015 Feb 11. PMID: 25673819.