Phillip G. Febbo, MD

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• Prostate Cancer

Department / Division:
Medicine / Medical Oncology

Address:
DUMC 3382
Durham, NC 27710

Appointment Telephone:
(919) 668-8108

Office Telephone:
(919) 668-8108

Fax Telephone:
(919) 668-7117

• M.D., University of California, San Francisco, 1993

• Internal Medicine, Brigham and Women's Hospital, Massachusetts, 1993-1996

• Dana Farber Cancer Institute, Massachusetts, 1996-1999

Clinical Interests:
Genitourinary oncology, clinical investigation, genomics

Research Interests:
The behavior of prostate cancer ranges widely from latent disease (i.e., confined to the prostate and discovered incidentally) to aggressive cancer that rapidly claims the life of the afflicted individual.  My research efforts at Duke’s Institute for Genome Science and Policy are focused on combining the best genomic technologies with our increasing biological understanding of prostate and other cancers in order to guide treatment for men diagnosed with localized and advanced disease.

At the Dana-Farber Cancer Institute, Harvard Medical School, and the Massachusetts Institute of Technology (MIT)’s Center for Genome Research (now the Broad Institute), I discovered that global gene expression can predict recurrence of prostate cancer following surgery (Cancer Cell, March 2002). Since then, our finding has been validated by four independent groups. This and additional work have demonstrated that DNA microarrays can sensitively and broadly detect variation in genetic expression and thereby monitor cellular biology. We are now testing the model in the setting of a national, prospective trial through a cooperative cancer group (CALGB 90203) and working to adapt this and similar models for clinical application; work that is supported by the National Cancer Institute and the Prostate Cancer Foundation.

My research also focuses on using computational analysis and in vitro methods to determine the activity and cellular function of specific signaling pathways in prostate cancer in order to identify the most appropriate therapy for diagnosed individuals (i.e. an agent that blocks the active pathway). The description and identification of pathway “signatures” within tumors remains a major challenge. Although studies where samples can be assayed before and after a therapy offer the best opportunity to develop such “signatures”, these trials are very difficult and in some situations not possible. Because of this, I have collaborated with William Hahn, MD, PhD, at the Dana-Farber Cancer Institute, to develop a genetically defined, cell-based model of prostate cancer and we have demonstrated that these cells mimic local and metastatic prostate cancer (Cancer Research, Dec 2004). In addition, I am collaborating with Sayan Mukherjee, PhD to apply and further develop the emerging computational tool of gene set enrichment analysis (GSEA) to important clinical and biological questions in prostate cancer.

Once a pathway signature is defined, we then use computational biology to identify if such signatures of activity are present in human tumors. To this end, we have refined our methods so that we can measure global gene expression using DNA chips on very small numbers of cells obtained following laser capture microdissection (LCM). This approach has allowed us to assay the biology of cells prior to and following treatment so as to determine 1) if a pathway is active? (i.e. is the signature present?), 2) did the signature change with treatment?, and 3) did the change in signature correlate with a response to therapy (i.e. did the patient’s tumor respond to the therapy?). This work has been and is currently supported in part by grants from the Damon Runyon Cancer Research Foundation and the Prostate Cancer Foundation.

This approach promises to match effective therapy with patients who have aggressive cancer and holds true potential to decrease the pain and suffering. We are very well positioned to identify and validate pathway signatures and test the significance of these signatures across different disease phenotypes such as treatment refractory metastatic adenocarcinoma. This research combines basic science, laboratory prostate cancer models, genomic technologies, computational science, and clinical trials in patients in order to improve care. Such an approach is only feasible within an integrated environment such as the Institute for Genome Science and Policy.

Representative Publications:
Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006 Mar 1;66(5):2815-25. (2006) Abstract

Febbo PG, Thorner A, Rubin MA, Loda M, Kantoff PW, Oh WK, Golub T, George D. Application of oligonucleotide microarrays to assess the biological effects of neoadjuvant imatinib mesylate treatment for localized prostate cancer. Clin Cancer Res. 2006 Jan 1;12(1):152-8. (2006) Abstract

Febbo PG, Kantoff PW. Noise and bias in microarray analysis of tumor specimens. J Clin Oncol. 2006 Aug 10;24(23):3719-21. (2006) Abstract

Edelman E, Porrello A, Guinney J, Balakumaran B, Bild A, Febbo PG, Mukherjee S. Analysis of sample set enrichment scores: assaying the enrichment of sets of genes for individual samples in genome-wide expression profiles. Bioinformatics. 2006 Jul 15;22(14):e108-16. (2006) Abstract

Balakumaran BS, Febbo PG. New insights into prostate cancer biology. Hematol Oncol Clin North Am. 2006 Aug;20(4):773-96. (2006) Abstract

Febbo PG, Richie JP, George DJ, Loda M, Manola J, Shankar S, Barnes AS, Tempany C, Catalona W, Kantoff PW, Oh WK. Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. Clin Cancer Res. 2005 Jul 15;11(14):5233-40. (2005) Abstract

Febbo PG, Lowenberg M, Thorner AR, Brown M, Loda M, Golub TR. Androgen mediated regulation and functional implications of fkbp51 expression in prostate cancer. J Urol. 2005 May;173(5):1772-7. (2005) Abstract

Bild A, Febbo PG. Application of a priori established gene sets to discover biologically important differential expression in microarray data. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15278-9. (2005) Abstract

Alvarez JV, Febbo PG, Ramaswamy S, Loda M, Richardson A, Frank DA. Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors. Cancer Res. 2005 Jun 15;65(12):5054-62. (2005) Abstract

Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, Loda M, Lane HA, Sellers WR. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med. 2004 Jun;10(6):594-601. (2004) Abstract

Berger R, Febbo PG, Majumder PK, Zhao JJ, Mukherjee S, Signoretti S, Campbell KT, Sellers WR, Roberts TM, Loda M, Golub TR, Hahn WC. Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells. Cancer Res. 2004 Dec 15;64(24):8867-75. (2004) Abstract

Singh D, Febbo PG, Ross K, Jackson DG, Manola J, Ladd C, Tamayo P, Renshaw AA, D'Amico AV, Richie JP, Lander ES, Loda M, Kantoff PW, Golub TR, Sellers WR. Gene expression correlates of clinical prostate cancer behavior. Cancer Cell. 2002 Mar;1(2):203-9. (2002) Abstract

Febbo PG, Kantoff PW, Platz EA, Casey D, Batter S, Giovannucci E, Hennekens CH, Stampfer MJ. The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer. Cancer Res. 1999 Dec 1;59(23):5878-81. (1999) Abstract

Febbo PG, Kantoff PW, Giovannucci E, Brown M, Chang G, Hennekens CH, Stampfer M. Debrisoquine hydroxylase (CYP2D6) and prostate cancer. Cancer Epidemiol Biomarkers Prev. 1998 Dec;7(12):1075-8. (1998) Abstract

Kantoff PW, Febbo PG, Giovannucci E, Krithivas K, Dahl DM, Chang G, Hennekens CH, Brown M, Stampfer MJ. A polymorphism of the 5 alpha-reductase gene and its association with prostate cancer: a case-control analysis. Cancer Epidemiol Biomarkers Prev. 1997 Mar;6(3):189-92. (1997) Abstract