Skip to Content

'
Isaiah J Fidler, DVM, PhD

Present Title & Affiliation

Primary Appointment

Director, Metastasis Research Laboratory, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
R. E. "Bob" Smith Distinguished Chair in Cell Biology, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Professor, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Professor, Department of Cancer Biology, Graduate School of Biomedical Sciences University of Texas Health Science Center, Houston, TX

Research Interests

  

Research in my laboratory continues to focus on the biology and therapy of cancer metastasis. Most recently, we have focused on the development and progression of brain metastasis. A large number of cancer patients develop metastasis to the brain. For untreated patients, the median survival is 1-2 months, and conventional radio-chemotherapy can extend the median survival to 4-6 months. The outcome of metastasis in general and brain metastasis in particular depends on the interaction of specific metastatic cells with host factors in the organ microenvironment (the “seed and soil” principle). 

 

Histological examination of clinical specimens of human breast, lung, melanoma, and colon brain metastases demonstrates that the lesions are surrounded and infiltrated by activated astrocytes expressing glial fibrillary acidic protein (GFAP). GFAP-positive astrocytes are also associated with experimental brain metastases produced in mice by lung, brain, melanoma, and colon cancers. We isolated astrocytes from the brain of the “ImmortoMouse” and established the cells in culture. Multiple in vitro studies conclude that astrocytes cocultured with tumor cells protect the tumor cells from chemotherapeutic agents (Taxol, VCR, VBL, 5-FU). Establishment of a gap junction between astrocytes and tumor cells is required for this chemoprotection. Coculture of tumor cells with other tumor cells or fibroblasts does not protect the cells from chemotherapeutic drugs. Microarray experiments for cross-species hybridization (human tumor cells cocultured with mouse astrocytes or mouse fibroblasts) identified upregulation of survival genes in tumor cells cocultured with astrocytes, but not with fibroblasts. Significantly, these survival genes were uniformly upregulated in different tumor cells (breast, lung) cocultured with astrocytes.

 

The role of astrocytes in physiology is to supply glucose and oxygen to neurons to assure their survival. Unfortunately, tumor cells that can proliferate in the brain parenchyma exploit astrocytes for these same functions. Since the development of metastases depends on the interactions of tumor cells with host factors, treatment of brain metastasis must be directed against both the tumor cells and the organ microenvironment.

Office Address

The University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd
Unit Number: Unit 173
Houston, TX 77030
Room Number: SRB1.123b

Education & Training

Degree-Granting Education

1970 University of Pennsylvania, Philadelphia, PHD, Pathology
1963 Oklahoma State University, Stillwater, OK, DVM, Veterinary Medicine
1961 Oklahoma State University, Stillwater, OK, BS, Veterinary Medicine

Experience/Service

Academic Appointments

Director, Department of Cancer Biology, Cancer Metastasis Research Center, Houston, TX, 1/1998-11/2010

Administrative Appointments/Responsibilities

Director, Cancer Metastasis Research Center, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 6/2008-11/2010
Department Chair, Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 1/1983-5/2008

Military or Other Governmental Service

Israel Defense Force, 1/1955-1/1957

Honors and Awards

2013-present Fellow, AACR Academy, American Assn. for Cancer Research
2013 2013 Medal of Honor Award for Basic Research, American Cancer Society
2010-present Annual I.J. "Josh" Fidler Innovation in Metastasis Research Award, Metastasis Research Society
2010-present Annual Isaiah J. Fidler Graduate Fellowship in Cancer Metastasis, GSBS
2010 Maimonides Award, State of Israel Bonds
2010 Nature Publishing Lifetime Achievement Award, Nature Publishing
2009 iSBTc Richard V. Smalley Memorial Lectureship Award, iSBTc
2007 AAAS Fellow, American Association for the Advancement of Science
2007 AVMA Honor Roll, American Veterinary Medical Association
2004 Charles A. LeMaistre Outstanding Achievement Award in Cancer, MDACC
1999 Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research
1993 City of Paris Medal of Vermeil
1988 G. H. A. Clowes Memorial Award

Selected Publications

Peer-Reviewed Original Research Articles

1. Langley RR, Fidler IJ. The seed and soil hypothesis revisited - the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer 128(11):2527-2535, 6/1/2011. e-Pub 3/25/2011. PMCID: PMC3075088.
2. Guo L, Langley RR, Fan D, Zhang F, Tsan R, Lee J-S, Fidler IJ. Selection of brain metastasis-initiating breast cancer cells according to growth on hard agar. American Journal of Pathology 178(5):2357-2366, 5/2011.
3. Kim SJ, Kim JS, Park ES, Lee JS, Lin Q, Langley RR, Maya M, He J, Kim SW, Weihua Z, Balasubramanian K, Fan D, Mills GB, Hung MC, Fidler IJ. Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy. Neoplasia 13(3):286-298, 3/2011. PMCID: PMC3050871.
4. Kim SJ, Kim JS, Kim SW, Brantley E, Yun SJ, He J, Maya M, Zhang F, Wu Q, Lehembre F, Regenass U, Fidler IJ. Macitentan (ACT-064992), a tissue-targeting endothelin receptor antagonist, enhances therapeutic efficacy of paclitaxel by modulating survival pathways in orthotopic models of metastatic human ovarian cancer. Neoplasia 13(2):167-179, 2/2011. PMCID: PMC3033595.
5. Tanaka T, Godin B, Bhavane R, Nieves-Alicea R, Gu J, Liu X, Chiappini C, Fakhoury JR, Amra S, Ewing A, Li Q, Fidler IJ, Ferrari M. In vivo Evaluation of Safety of Nanoporous Silicon Carriers Following Single and Multiple Dose Intravenous Administrations in Mice. Int J Pharm 402(1-2):190-197, 12/15/2010. e-Pub 9/29/2010. PMCID: PMC2982888.
6. Fidler IJ, Balasubramanian K, Lin Q, Kim SW, Kim SJ. The brain microenvironment and cancer metastasis. Mol Cells 30(2):93-98, 8/2010. e-Pub 8/19/2010. PMID: 20799011.
7. Kuo HP, Lee DF, Chen CT, Liu M, Chou CK, Lee HJ, Du Y, Xie X, Wei Y, Xia W, Weihua Z, Yang JY, Yen CJ, Huang TH, Tan M, Xing G, Zhao Y, Lin CH, Tsai SF, Fidler IJ, Hung MC. ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway. Sci Signal 3(108):ra9, 2010. e-Pub 2/9/2010. PMCID: PMC2874891.
8. Kim SJ, Kim JS, Papadopoulos J, Wook Kim S, Maya M, Zhang F, He J, Fan D, Langley R, Fidler IJ. Circulating macrophages expressing CD31: implications for acute and chronic angiogenesis. Am J Pathol 174(5):1972-1980, 5/2009. e-Pub 4/6/2009. PMCID: PMC2671284.
9. Zhang C, Zhang F, Tsan R, Fidler IJ. Transforming growth factor-beta2 is a molecular determinant for site-specific melanoma metastasis in the brain. Cancer Res 69(3):828-835, 2/1/2009. e-Pub 1/13/2009. PMCID: PMC2633423.
10. Weihua Z, Tsan R, Huang WC, Wu Q, Chiu CH, Fidler IJ, Hung MC. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell 13(5):385-93, 5/2008. PMCID: PMC2413063.
11. Weihua Z, Tsan R, Schroit AJ, Fidler IJ. Apoptotic cells initiate endothelial cell sprouting via electrostatic signaling. Cancer Res 65(24):11529-35, 12/2005. PMCID: PMC1404497.
12. Fidler IJ. The organ microenvironment and cancer metastasis. Differentiation 70(9-10):498-505, 12/2002. PMID: 12492492.
13. Fidler IJ. Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res 50(19):6130-8, 10/1990. PMID: 1698118.
14. Schackert G, Fidler IJ. Site-specific metastasis of mouse melanomas and a fibrosarcoma in the brain or meninges of syngeneic animals. Cancer Res 48(12):3478-84, 6/1988. PMID: 3370643.
15. Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science 217(4564):998-1003, 9/1982. PMID: 7112116.
16. Talmadge JE, Wolman SR, Fidler IJ. Evidence for the clonal origin of spontaneous metastases. Science 217(4557):361-3, 7/1982. PMID: 6953592.
17. Fidler IJ, Kripke ML. Metastasis results from preexisting variant cells within a malignant tumor. Science 197(4306):893-5, 8/1977. PMID: 887927.
18. Fidler IJ. Selection of successive tumour lines for metastasis. Nat New Biol 242(118):148-9, 4/1973. PMID: 4512654.
19. Fidler IJ. Metastasis: quantitative analysis of distribution and fate of tumor embolilabeled with 125 I-5-iodo-2'-deoxyuridine. J Natl Cancer Inst 45(4):773-82, 10/1970. PMID: 5513503.

Invited Articles

1. Fidler IJ. Biologial heterogeneity of cancer -- implication to therapy (Commentary). Human Vaccines and Immunotherapeutics 8(8):1141-1142, 8/2012.
2. Fidler IJ. The role of the organ microenvironment in brain metastasis. Semin Cancer Biol 21(2):107-112, 4/2011. e-Pub 12/16/2010. PMID: 21167939.
3. Talmadge JE, Fidler IJ. AACR Centennial Series: The biology of cancer metastasis: historical perspective. Cancer Res 70(14):5649-5669, 7/15/2010. e-Pub 7/7/2010. PMID: 20610625.

Book Chapters

1. Fidler IJ, Kripke ML. The biology of cancer metastasis. In: Cancer - The Outlaw Cell, 3. Ed(s) LaFond R. Oxford University Press: New York, NY, 198-210, 2012.

Grant & Contract Support

Title: Therapy of Liver Metastases via Multi-stage System
Funding Source: NIH/NCI
Role: Project Leader
Principal Investigator: Mauro Ferrari
Duration: 9/28/2009 - 7/31/2014
 
Title: The Role of Endothelin in Progressive Growth and Metastasis of Neoplasms
Funding Source: Actelion Pharmaceuticals, Ltd.
Role: Principal Investigator
Duration: 1/1/2008 - present

Last updated: 8/27/2013