Wolf Prize Laureate in Medicine 2010
Affiliation at the time of the award:
Max Planck Institute of Biochemistry, Germany
“for his pioneering contributions to the discovery and characterization of human proto-onco-genes and the development of novel cancer therapies”.
Professor Axel Ullrich (born 1943, Germany) and colleagues reported the cloning of the cDNA encoding the epidermal growth factor receptor (EGFR), in 1984. This opened up the field of Signal Transduction research. Subsequently, Ullrich confirmed the existence of animal oncogene-related human proto-oncogenes, by cloning the human homologs of v-fms and v-kit; and thereby establishing “cancer targets” for therapy development, at a very early stage.
In 1985, the discovery by Ullrich and his collaborators, of an EGFR-related gene, HER2/c-erbB2, led to Herceptin, the first cancer therapeutic based on genome research. Ullrich initiated collaboration with Dennis Slamon, towards the genomic analysis of primary breast tumors, which led to the discovery that the gene encoding HER2 is amplified and over-expressed in 25 percent of all breast cancers; and that HER2 amplification predicts rapid disease progression. Ullrich’s laboratory then developed monoclonal antibodies for HER2, one of which, MAb 4D5, was subsequently humanized and developed by Genentech, Inc. as a therapeutic for the treatment of metastatic breast cancer for patients with HER2 gene amplification in their tumor cells. Herceptin was approved by the FDA in 1998 and represents the first targeted therapeutic agent that was developed on the basis of a newly discovered gene with an oncogenic function in human cancer.
Ullrich’s second translational project, leading to an FDA-approached cancer therapy, began with the discovery and functional characterization of the receptor tyrosine kinase Flk-1/VEGFR2, as an essential element of the process of tumor angiogenesis. Ullrich’s laboratory demonstrated that blocking this receptor in a mouse brain tumor model, resulted in significantly impaired tumor growth. This approach led to the development of SU11248 (a.k.a. SUTENT/Sunitinib), which was approved by the FDA and the European EMEA, for the treatment of kidney carcinoma and gastro-intestinal stromal tumors, in 2006. SUTENT mediates its therapeutic effects not only through the inhibition of angiogenesis, but also through the interference with multiple kinase targets of cancer cells, while being well proven to be well tolerated by patients. Basic research in Ullrich’s laboratory also led to the characterization of several other medically relevant receptor proteins, including PDGFR, CSF1R, insulin receptor, IGF1R and SCFR/c-kit. Following the prototypical examples of Herceptin and SUTENT, drugs that interfere with the disease-promoting functions of receptor tyrosine kinases are currently being developed in Ullrich´s laboratory and in pharmaceutical companies worldwide. With more than 70,000 citations, he is one of the most frequently cited scientists, in the rapidly progressing era of science of the last 30 years. Prof. Ullrich´s work is an exceptional triumph for biomedical research and has proven its power and benefit to hundreds of thousands of cancer patients.