Pnina Brodt
- Professor - Dept. of Surgery, Oncology and Medicine
- Senior Scientist- Research Institute - 91社区 Health Center
- Co-leader of the Cancer Axis 鈥� 2009-2015
- Cancer Research Laboratory Director
M.Sc., Ph.D.
The following projects are currently ongoing in the Brodt lab (please see detailed description below):
1. Sex disparity and the role of estrogen in the microenvironment of liver metastases
2. Optimizing delivery of the IGF-Trap to the brain for the treatment of glioblastoma
3. Combinatorial immunotherapy for pancreatic ductal adenocarcinoma
4. The role of IMP1 in pancreatic ductal adenocarcinoma progression and liver metastasis.
Our research has focused on the biology of cancer metastasis. In this context, our work has centered on the role of the microenvironment (ME) in liver metastasis (LM) of GI and lung cancer. Our overarching goal has been translational with an aim to identify targets and develop therapeutic interventions to block the spread of malignant disease to, and within the liver. In the course of these studies, our research team was among the first to show that cancer cells entering the liver induce a rapid inflammatory response, resulting in a cytokine cascade that enables trans-endothelial migration and liver colonization. We showed that in this TNF-飦� rich ME, the metastatic cells escape death through autocrine IL-6/STAT3 signaling while the TNF receptor TNFR2 was identified as a survival factor for regulatory T cells (Treg) and myeloid derived suppressor cells (MDSC) in the immune-tolerant ME (IME) of LM. Our team was also among the first to document the importance of the IGF axis to cancer cell invasion and metastasis in general, and LM, in particular. Several strategies for targeting the IGF axis were developed, leading to the bioengineering of the IGF-Trap - a potent inhibitor of growth and metastasis of several aggressive cancers including colon cancer, lung cancer and pancreatic ductal adenocarcinoma (PDAC). More recently, we found that the IGF-Trap affects the innate immune response to metastatic cells in the liver. Our work on PDAC also led us to identify a novel interaction between the pancreatic and hepatic stellate cells that leads to the formation of pre-metastatic niches in the liver, thereby promoting PDAC liver metastasis. More recently, we have begun testing the therapeutic effect of the IGF-Trap in orthotopic models of glioma using novel strategies for overcoming the brain blood barrier and effectively delivering this drug to the brain.
Selected Peer-reviewed articles (2016-2021)
Tsilimigras DI, Brodt P, Clavien PA, Muschel RJ, D'Angelica MI, Endo I, Parks RW, Doyle M, de Santiba帽es E, Pawlik TM. Liver Metastases. Nat Rev Dis Primers 7(1):27. doi: 10.1038/s41572-021-00261-6.
Tsui J, Qi S, Perrino S, Leibovitch M., and Brodt P. Identification of a Resistance Mechanism to IGF-IR Targeting in Human Triple Negative MDA-MB-231 Breast Cancer Cells. 11(4): 527. Published online 2021 Apr 1. doi:
Samani AA, Nalbantoglu J, Brodt P. Glioma Cells With Genetically Engineered IGF-I Receptor Downregulation Can Persist in the Brain in a Dormant State. Front Oncol. 2020 Sep 23;10:555945. doi: 10.3389/fonc.2020.555945. eCollection 2020.
Vazana U, Schori L, Monsonego U, Swissa E, Pell GS, Roth Y, Brodt P, Friedman A, Prager O. TMS-Induced Controlled BBB Opening: Preclinical Characterization and Implications for Treatment of Brain Cancer. Pharmaceutics. 2020 Oct 5;12(10):E946. doi: 10.3390/pharmaceutics12100946.
Ciner AT, Jones K, Muschel RJ, and Brodt P., The unique immune microenvironment of liver metastases: Challenges and opportunities. Semin Cancer Biol. 2020 Jun 8:S1044-579X(20)30138-3. doi: 10.1016/j.semcancer.2020.06.003.
Chen, YM., Qi, S., Perrino, S., Hashimoto, M. and Brodt, P., Targeting the IGF-Axis for Cancer Therapy: Development and Validation of an IGF-Trap as a Potential Drug, Cells 2020 Apr 29;9(5):E1098. doi: 10.3390/cells 9051098.
Qi, S., Perrino, S., Miao, X., Lamarche-Vane, N., Brodt, P., The Chemokine CCL7 Regulates Invadopodia Maturation and MMP-9 Mediated Collagen Degradation in Liver-Metastatic Carcinoma Cells, Cancer Lett 2020 Mar 23. pii: S0304-3835(20)30137-3. doi: 10.1016/j.canlet.2020.03.018.
Milette, S., Hashimoto, M.,P茅rrino,S., Qi, S., Chen, M., Ham, B., Wang,N., Istomine, R.,Lowy,AM., Piccirillo,C. and Brodt, P., Sexual Dimorphism and the Role of Estrogen in the Immune Microenvironment of Liver Metastases, Nat Commun. 2019 Dec 17;10(1):5745. doi: 10.1038/s41467-019-13571-x.
Vaniotis, G., Moffett, S., Sulea, T., Wang, N., Elahi, S.M., Lessard, E., Baardsnes, J., Perrino, S., Durocher, Y., Frystyk, J., Massie, B., and Brodt, P. Enhanced anti-metastatic bioactivity of an IGF-TRAP re-engineered to improve physicochemical properties, Sci Rep., 8(1):17361-17374, 2018, doi: 10.1038/s41598-018-35407-2.
Vaniotis, G., Rayes, RF., Qi, S., Milette, S., Wang, S., Perrino, S., Nystr枚m, N., He, Y., Lamarche-Vane, N., and Brodt, P. Collagen IV-conveyed signals regulate cytokine production and promote liver metastasis, Oncogene 37(28): 3790-3805, 2018, doi: 10.1038/s41388-018-0242-z. Epub 2018 Apr 13.
Van Dam, P-J, Van der Stok, EP., (+ 27 authors), Brodt P., Reynolds AR and Vermeulen, PB. International consensus guidelines for scoring the histopathological growth patterns of liver metastasis- British Journal of Cancer, 117(10):1427-1441, 2017, doi: 10.1038/bjc.2017.334. Epub 2017 Oct 5.
Milette, S., Sicklick, J.K., Lowy, AM., and Brodt P., Molecular Pathways: Targeting the microenvironment of liver metastases. Clin. Cancer Research 鈥� 2017, doi: 10.1158/1078-0432.CCR-15-1636. Epub 2017 Jun 14. Review.
Fernandez, M.C., Rayes, R., Ham, B., Wang, N., Bourdeau, F., Xu, J., Kisselova, T. and Brodt, P. (2016). The type I Insulin-like growth factor regulates the liver stromal response to metastatic colon carcinoma cells. Oncotarget 8(32): 52281鈥�52293, 2017, doi: 10.18632/oncotarget.12595. eCollection 2017 Aug 8.
Brodt, P., Role of the microenvironment in liver metastasis: from pre- to prometastatic niches- Clinical Cancer Research -Invited review, 15;22(24): 5971-5982, 2016, Epub 2016 Oct 19.
Ham, B., Fernandez, M.C., D鈥機osta, Z. and Brodt, P. The diverse roles of the TNF axis in cancer progression and metastasis. Trends in Cancer Research - Invited Review, 11:1-27, 2016