Branimir Ivan Sikic

Branimir I. Sikic

Branimir Ivan "Brandy" Sikic (born October 18, 1947[1]) is an American medical doctor and scientist at Stanford University School of Medicine. He is an oncologist and cancer pharmacologist, and has served as a faculty member at Stanford University since 1979. His research spans basic, translational, and clinical research and investigates the mechanisms of drug resistance and the development of new anticancer therapies.

Early life

Sikic was born in Graz, Austria, on October 18, 1947. His parents were refugees from Croatia, his father a mathematician and his mother a linguist. The family emigrated to Adelaide, Australia in 1949, and to Cincinnati, Ohio in 1956.[2] Sikic graduated from St. Xavier High School as president of his class in 1964 at age 16,[3] and attended Georgetown University in Washington, D.C., where he obtained a B.S. degree in biology in 1968.[4]

Education and training

Sikic attended the University of Chicago Pritzker School of Medicine, graduating with an M.D. in 1972. He returned to Georgetown University Hospital in Washington, D.C. for an internship and residency in internal medicine (1972-5). From 1975 to 1978 he was a postdoctoral laboratory research fellow at the National Institutes of Health (NIH), working on the regulation of drug metabolism and the pharmacology and pulmonary toxicology of the anticancer drug bleomycin. He returned to Georgetown in 1978–9 to complete a clinical fellowship in medical oncology, prior to joining the faculty at Stanford University.[4]

Honors and awards

In 1992 Sikic began directing the General Clinical Research Center and then the Center for Clinical and Translational Research[5] in 2008. He is the founder and director of the Central European Oncology Congress held in Opatija, Croatia since 1998. On January 9, 2010, he was awarded the Katarina Zrinska Medal for Science and Medicine by the President of Croatia.[6]

Contributions to science

Mechanisms and regulation of multidrug resistance

Sikic has made significant contributions to understanding the biology and clinical significance of multidrug resistance (MDR), particularly the P-glycoprotein (P-gp) multidrug transporter and regulation of the ABCB1 gene.[7] He discovered that deletion of aa335 changes the drug-binding spectrum and is integral to the pharmacophore of P-gp.[8] He also defined specific sites of transactivation of ABCB1, and mechanisms of amplification of the gene.[9][10]

Clinical trials of modulation of multidrug resistance

The laboratory work on drug resistance mechanisms led to a series of clinical Phase I-III trials that defined this field.[11] Early on, Sikic's group found that P-gp inhibition resulted in significant pharmacokinetic alterations of several anticancer drugs, with the potential for markedly increased toxicities unless doses were adjusted.[12] These findings, and the co-existence of other resistance mechanisms in human cancers, redefined the field and demonstrated the limited clinical utility of MDR modulation.[13][14]

Cancer genomics

The Sikic group utilized gene expression profiling and systems biology to yield insight into cancer taxonomy and prognostic and predictive signatures for cancer therapies.[15][16][17] With their colleagues Olivier Gevaert and Sylvia Plevritis, they have identified driver genes for ovarian cancers.[18][19]

See also

• SPECTRUM: Clinical & Translational Research Unit
• Cancer Molecular Therapeutics Research Association (CMTRA)

References

1. Sikic, Branimir Ivan. "Branimir I. (Brandy) Sikic, M.D." (curriculum vitae). Stanford, California: Stanford University School of Medicine. Retrieved April 29, 2023.
2. "Goodbye Dear Old Homeland" by Yasna Sikic Hood
3. "Alumni X-Cerpts". St. Xavier High School Magazine. Cincinnati: St. Xavier High School. Fall 2015. p. 16 – via issuu.
4. "Branimir I. Sikic, M. D." CAP Profiles. Stanford, California: Stanford University School of Medicine. August 12, 2021. Retrieved January 15, 2023.
5. Newby, Kris. "New Freidenrich Center will help streamline clinical research" (Press release). Stanford, California: Stanford Center for Clinical and Translational Research and Education. Retrieved 2023-01-15.
6. Brandt, Michelle (February 8, 2010). "President of Croatia honors work of Stanford oncologist" (Press release). Stanford, California: Stanford University School of Medicine. Retrieved April 29, 2023.
7. Chen, G; Duran, GE; Steger, KA; Lacayo, NJ; Jaffrezou, JP; Dumontet, C; Sikic, BI (1997). "Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered phenotype, and resistance to cyclosporins". Journal of Biological Chemistry. 272 (9): 5974–82. doi:10.1074/jbc.272.9.5974. PMID 9038218.
8. Chen, GK; Sale, S; Tan, S; Ermoian, RP; Sikic, BI (2004). "CCAAT/enhancer-binding protein beta (nuclear factor for interleukin 6) transactivates the human MDR1 gene by interaction with an inverted CCAAT box in human cancer cells". Molecular Pharmacology. 65 (4): 906–16. doi:10.1124/mol.65.4.906. PMID 15044620. S2CID 86591291.
9. Chen, KG; Wang, YC; Schaner, ME; Francisco, B; Duran, GE; Juric, D; Huff, LM; Padilla-Nash, H; Ried, T; Fojo, T; Sikic, BI (2005). "Genetic and epigenetic modeling of the origins of multidrug resistant cells in a human sarcoma cell line". Cancer Research. 65 (20): 9388–97. doi:10.1158/0008-5472.CAN-04-4133. PMID 16230402.
10. Chen, KG; Sikic, BI (2012). "Molecular pathways: regulation and therapeutic implications of multidrug resistance". Clinical Cancer Research. 18 (7): 1863–9. doi:10.1158/1078-0432.CCR-11-1590. PMC 3359695. PMID 22344233.
11. Yahanda, AM; Adler, KM; Fisher, G; Brophy, NA; Hardy, R; Halsey, J; Gosland, MP; Lum, BL; Sikic, BI (1992). "A phase I trial of etoposide with cyclosporine as a modulator of multidrug resistance". Journal of Clinical Oncology. 10 (10): 1624–34. doi:10.1200/JCO.1992.10.10.1624. PMID 1403040.
12. Lum, BL; Kaubisch, S; Yahanda, AM; Adler, KM; Jew, K; Ehsan, MN; Halsey, J; Gosland, MP; Sikic, BI (1992). "Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial of modulation of multidrug resistance". Journal of Clinical Oncology. 10 (10): 1635–42. doi:10.1200/JCO.1992.10.10.1635. PMID 1403041.
13. Bartlett, NL; Lum, BL; Fisher, GA; Brophy, NA; Ehsan, MN; Halsey, J; Sikic, BI (1994). "A phase I trial of doxorubicin with cyclosporine as a modulator of multidrug resistance". Journal of Clinical Oncology. 12 (4): 835–42. doi:10.1200/JCO.1994.12.4.835. PMID 8151326.
14. Advani, R; Lum, BL; Fisher, GA; Halsey, J; Chin, DL; Jacobs, CD; Sikic, BI (2005). "A phase I trial of liposomal doxorubicin, paclitaxel, and valspodar (PSC-833), an inhibitor of multidrug resistance". Annals of Oncology. 16 (12): 1968–73. doi:10.1093/annonc/mdi396. PMID 16126736.
15. Juric, D; Lacayo, NJ; Ramsey, MC; Racevskis, J; Wiernik, PH; Rowe, JM; Goldstone, AH; O'Dwyer, PJ; Paietta, E; Sikic, BI (2007). "Differential gene expression patterns and interaction networks in BCR/ABL positive and negative adult acute lymphoblastic leukemias". Journal of Clinical Oncology. 25 (11): 1341–9. doi:10.1200/JCO.2006.09.3534. PMID 17312329.
16. Bredel, M; Scholtens, DM; Harsh, GR; Bredel, C; Chandler, JP; Renfrow, JJ; Yadav, AK; Vogel, H; Scheck, AC; Tibshirani, R; Sikic, BI (2009). "A network model of a cooperative genetic landscape in brain tumors". Journal of the American Medical Association. 302 (3): 261–75. doi:10.1001/jama.2009.997. PMC 4447713. PMID 19602686.
17. Schaner, Me; Ross, DT; Ciaravino, G; Sorlie, T; Troyanskaya, O; Diehn, M; Wang, YC; Duran, GE; Sikic, TL; Caldeira, S; Skomedal, H; Tu, IP; Hernandez-Boussard, T; Johnson, SW; O'Dwyer, PJ; Fero, MJ; Kristensen, GB; Borresen-Dale, AL; Hastie, T; Tibshirani, R; Van De Rijn, M; Teng, NN; Longacre, TA; Botstein, D; Brown, PO; Sikic, BI (2003). "Gene expression patterns in ovarian carcinomas". Molecular Biology of the Cell. 14 (11): 4376–86. doi:10.1091/mbc.E03-05-0279. PMC 266758. PMID 12960427.
18. Gevaert, O; Villalobos, V; Sikic, BI; Plevritis, SK (2013). "Identification of ovarian cancer driver genes by using module network integration of multi-omics data". Interface Focus. 3 (4): 2013.0013. doi:10.1098/rsfs.2013.0013. PMC 3915833. PMID 24511378.
19. Willis, S; Villalobos, VM; Gevaert, O; Abramovitz, M; Williams, C; Sikic, BI; Leyland-Jones, B (2016). "Single gene prognostic biomarkers in ovarian cancer: a meta-analysis". PLOS ONE. 11 (2): e.0149183. Bibcode:2016PLoSO..1149183W. doi:10.1371/journal.pone.0149183. PMC 4757072. PMID 26886260.