2008 - Axel Ullrich

Director, Department of Molecular Biology, Max Planck Institute of Biochemistry
Martinsried, Germany

Motivation:
Dr. Axel Ullrich has been named the recipient of the 2008 award for his pioneering work in the translation of molecular genetic research into biomedical applications. His fundamental discoveries in signal transduction research led to novel insight into the genomic determinants that promote cancer progression and to the development of novel cancer treatments including the FDA approved therapeutics Herceptin and /TENT/Sunitinib.
During the very early stages of gene technology development, Dr. Dr. Ullrich and his colleagues were the first to cline the genes encoding medically important proteins including the precursor to insulin. This led to the development of Humulin, the first therapeutic agent to be developed through recombinant DNA technology.
Following up on his early work on insulin and growth factors, Dr. Ullrich subsequently focused his efforts on the cDNA cloning of growth factor receptors. In a landmark paper published in 1984, Dr. Ullrich and colleagues reported the primary structure of the receptor for the human epidermal growth factor, the first cell surface receptor to be molecularly cloned. That study also provided formal proof that the avian v-erbB oncogene was a structurally altered homologue of human EGFR and identified EGFR gene amplification the cause for aberrant EGFR expression in the A431 cancer cell line. The latter findings provided the proof of concept that genomic alterations could lead to aberrant signal generation in human cancer cells, via structural changes and/or overexpression of genes encoding growth factor receptors. By collaborating with a number of colleagues, Dr. Ullrich went on to establish the proto-oncogene function of the human homologs of v-fms and v-kit by cDNA cloning of CSF-1 and SCR receptor tyrosine kinases and growth factor receptors for insulin, PDGF and IGF-1. These studied paved the way to the molecular genetic analysis of growth factor receptors as human cancer genes and ushered in the modern era of signal transduction research.
This restless and visionary quest to understand the molecular pathogenesis of neoplastic disorders, Dr. Ullrich set up a collaborative effort with Dr. Dennis Slamon aimed at investigating the clinical relevance of structural alterations of RTK genes in human tumors. This team work led to the groundbreaking discovery that the HER2/ERBB2 gene is amplified and overexpressed in about 25% of all breast cancers and the HER2 amplification predicts rapid disease progression. This seminal finding prompted Dr. Ullrich to develop monoclonal antibodies capable of antagonizing HER2 oncogenic function, an effort that culminated years later with the production of Herceptin. The generation of Herceptin is to be regarded as the first successful attempt to develop a biological drug against an oncogene with a documented pathogenic role in human cancer. The strategy of genomics-based, target-driven drug development pioneered by Dr. Ullrich has revolutionized medicine and is now being pursued by hundreds of investigators.
Dr. Ullrich’s recent work led to two more seminal contributions, namely the development of SU1128/SUTENT, the first multi-targeted kinase inhibitor to gain FDA approval for cancer therapy, and the elegant identification of the molecular mechanisms responsible for the trans-activation of HER receptors by GPCRs.