Awardee 2014

Alexander Levitzki

for his work on the discovery of signal transduction therapy



Prof. Alexander Levitzki is a biochemist by training, and has been working since more than 45 years in the field of signal transduction and with a focus on cancer since the mid 1980s. His exceptional scientific achievements were the discovery and development of a large variety of low molecular weight selective inhibitors of Tyrosine Kinases. This served as the scientific basis for the subsequent development of an entirely new class of anticancer drugs, Gleevec by Novartis, Iressa by Astra Zeneca and Sutent by Sugen. Tyrosine Kinases are important mediators of the signaling cascade, determining key roles in diverse biological processes like growth, differentiation, metabolism and apoptosis, in response to external and internal stimuli. Genetic alterations, including point mutations, gene amplifications and chromosomal translocations, can render Tyrosine Kinases oncogenic properties. In the 1980’s Prof. Levitzki was the first to introduce the idea that one can generate selective inhibitors of EGF receptor kinase stopping EGF dependent proliferation of cancer cells (1988). This was followed by developing inhibitors of Her-2 (1991), Bcr-Abl (1992) PDGFR (1994) VEGFR2 (1996) and Jak2 (1996). When Levitzki started his work the dogmatic view was that due to the conservation of the structure of the kinase domain it would be impossible to generate selective kinase inhibitors. Nevertheless, Prof. Levitzki did not discourage and continued his dedicated research, finally proving that he could successfully discover and develop novel Tryosine Kinase inhibitors. He named them Tyrphostins (Tyrosine Phosphorylation Inhibitors) and also coined the term of what is known today as “Signal Transduction Therapy”, the foundation of the field of personalized cancer medicine.
Prof. Levitzki’s work has not only inspired the scientific community, as demonstrated by the large number of scientific citations (more than 24.000) but also attracted the attention of large Pharmaceutical companies, such as Novartis and Pfizer. They started crash programs devoting large resources to preparing synthetic Tyrosine Kinase inhibitors, finally succeeding in Gleevec, the first selective Bcr-Abl inhibitor for Chronic Meylogenous Leukemia (CML). Levitzki continued his pioneering work and with the company Sugen he developed Vascular Endothelial Growth Factor Receptor, (VEGFR2) kinase inhibitors as anti-angiogenic agents for the treatment of cancer. His work on VEGFR2 kinase inhibitor, with Axel Ullrich at Sugen, led to Sutent (Sunitinib), approved by the FDA to treat renal cell carcinoma. These remarkable series of discoveries continued with new inhibitors against other important oncogenic kinases such as Jak-2, IGF1R, EGFR and Her-2.
Importantly, Prof. Levitzki’s discoveries have also opened novel therapeutic options for other diseases, such as restenosis and Psoriasis and diagnostic EGFR inhibitors for PET imaging. In the past 8 years Prof. Levitzki expanded his fundamental work and has been developing chemical vectors homing to cancer cells that overexpress receptors that internalize, and deliver long chain synthetic double stranded RNA, leading to tumor inhibition and tumor eradication.

Presentation of Prof. Alexander Levitzki
(mp4 movie 35mb)

Presentation of Prof. Alexander Levitzki (mp4 movie 113mb)

Presentation of Prof. Alexander Levitzki (mp4 movie 113mb)


1963 M .Sc. in Chemistry and Bacteriology (Biochemistry Major)
Summa cum Laude
The Hebrew University of Jerusalem, Israel
1968 Ph.D. in Chemistry (Biochemistry and Biophysics)
Summa cum Laude
The Hebrew University of Jerusalem, Israel and The Weizmann Institute of Science, Rehovot
1968-1971 Post-doctoral Fellow, Department of Biochemistry,
University of California at Berkeley, Berkeley,
California, with Professor D. E. Koshland, Jr.
   
Academic Appointments
   
The Weizmann Institute of Science
1970 Senior Scientist, Department of Biophysics
1974-1976 Associate Professor (tenured).
   
The Hebrew Universlty of Jerusalem
1973 Associate Professor
1976 Professor
   
Foreign Appointments
   
1974
Visiting Professor of Chemistry, The University of
Oregon, Eugene, Oregon
1974
Visiting Professor of Biochemistry, University of
California at Berkeley
1979-1980
Visiting Scientist, The National Cancer Institute,
National Institutes of Health, Bethesda, Maryland
1984-1985
Fogarty Scholar-in-Residence, National Institutes of
Health, Bethesda, MD
1994-1995
Visiting Scholar, Stanford University, Stanford,
Califomia
2001, 2002, 2004
Visiting Professor, Comprehensive Cancer Center,
UCSF, San Francisco
 


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