Invention: Next-generation cancer treatments and breakthroughs in laboratory genetics
Scientific understanding of the genetic and cellular causes of cancer and other diseases has taken a quantum leap thanks to German molecular biologist Axel Ullrich. In a research career spanning four decades, Ullrich has pioneered new classes of medical treatment – including growth-inhibiting drugs for breast, intestinal and kidney cancer.
Prior to Ullrich's new methods, doctors had been searching for therapies that target cancer without causing the damage to healthy tissue that chemotherapy and radiation do. Based on new insight into signal transduction - the processes by which cells in the human body communicate - Ullrich developed next-generation drugs that stop cancer at the root by disrupting those cellular communication processes. Over the past 20 years, pharmaceuticals brought to market by Ullrich have included Herceptin, which is effective against breast cancer caused by the HER2 oncogene, a genetic trigger that Ullrich discovered, and a "tumour-starving" drug called Sunitinib.
Respected as an international authority in his field, Ullrich has held key positions at pharmaceutical development companies including Genentech. He has also spearheaded a new school of genetic research focused on signal transduction as director of the Molecular Biology department at the Max Planck Institute of Biochemistry in Martinsried, Germany. Ullrich's breakthroughs came as early as 1977, with the world's first transfer of the human insulin gene into bacteria, which spawned the world's first genetically engineered drug, recombinant human insulin, in 1982.
Breast cancer remains the most common cancer to affect women, and the World Health Organization (WHO) estimates that worldwide over 508 000 women succumbed to the disease in 2011. While survival rates have greatly improved over the past decade - they currently stand at 80% or higher in North America, Sweden and Japan - treatment of the disease can take a heavy toll on patients, especially because of the side effects of chemotherapy. Patients that test positive for certain genetic markers now benefit from targeted therapies of unprecedented efficacy, based on Ullrich's key insights into the genetic causes of disease formation.
Released in 1998, Ullrich's anti-breast cancer drug has been found to decrease tumour recurrence by 50% in women whose tumours express the HER2 oncogene. However, while Ullrich's findings provide the foundation for targeted therapies, scientists are only beginning to understand the full scope of human DNA. Currently, more than 1 800 disease genes have been identified and more than 2 000 genetic tests have become available, yet there are a total of 20 000 genes in the human genome. A fervent advocate of advancing understanding of disease-causing genes, Ullrich supports the search for further genetic markers of cancers through global research initiatives such as the Singapore Oncogenome Project.
Aside from holding key positions in commercial drug development at international pharmaceutical companies such as Genentech, Ullrich has launched several successful start-up companies, including Sugen in 1991 (bought by Pfizer), Axxima Pharmaceuticals in 1998 (now GPC Biotech AG), U3 Pharma in 2001 (now Daiichi Sankyo Company Ltd.), Kinaxo Biotechnologies GmbH in 2005 (now part of Evotec AG) and Blackfield AG in 2012.
Ullrich's next-generation pharmaceuticals have proven to be blockbuster drugs. Herceptin has ranked among the top 50 medications, with annual sales of up to EUR 6.3 billion before the patent expired in 2014. Sunitinib, marketed by Pfizer, is poised to generate annual sales of up to EUR 1.5 billion by 2018.
The world market for cancer drugs is expected to see considerable growth from EUR 72 billion in 2015 to EUR 103 billion by 2020. Kinase inhibitor drugs for treating cancer - a field pioneered by Ullrich - are expected to net approximately EUR 29 billion annually by 2019.
Axel Ullrich (right) pictured with a researcher at the Max Planck Institute in Martinsried, Germany
Axel Ullrich holding a test tube containing a cancer-stopping drug
How it works
Ullrich's "tumour-starving" medications work by cutting off the blood supply to cancerous tumours, thereby stopping their growth. This is achieved by "silencing" specific cellular signalling processes, including so-called protein tyrosine kinase gene transcripts.
These scripts send signals to the vascular endothelial growth factor receptor, which regulates the formation of new tumour blood vessels. Without new blood vessels, tumour growth ceases and patients can recover.
Ullrich's anti-breast cancer drug Herceptin targets tumours with a particular type of breast cancer gene, known as HER2. These HER2-positive cancer cells grow and multiply whenever HER2 receptors on their cell surface receive growth signals. Herceptin disrupts this process by attaching itself to the receptors, thereby "jamming" the reception of such signals.
After earning his PhD in molecular genetics from the University of Heidelberg in 1975, Ullrich found his calling during postdoctoral research at the University of California in San Francisco. In a laboratory equipped with some of the world's first molecular tools in genetic research, Ullrich became the first scientist to transfer a copy of the human insulin gene to bacteria in 1977.
More breakthroughs have followed during Ullrich's professional career. In 1978, as one of the first employees of biotech company Genentech in San Francisco, Ullrich made key discoveries in oncogenes and cellular disease genesis. In 1988, he returned to Germany and continued his research as director of the Molecular Biology department at the Max Planck Institute of Biochemistry in Martinsried.
Regarded as an international authority in genetics, particularly in the emerging research field of signal transduction, Ullrich is listed as the inventor on well over 100 patents filed worldwide. A prolific author, with over 570 scientific publications to his name, he is among the ten most-cited scientists of the past 25 years with at least 50 000 citations. His scientific achievements have earned him some of the world's highest honours, including the Robert Koch Prize (2001), the Clifford Prize for Cancer Research (2005), the Hamdan Award for Medical Research Excellence (2008) and the Wolf Prize in Medicine (2010). He is one of twelve scientists to have been inducted into the German Research Hall of Fame.
Did you know?
There are about 20 000 different protein-coding genes in the human genome. Their role in the formation of diseases has been uncovered by genetic breakthroughs since the first mapping of human DNA in 2001 by the Human Genome Project. Although mapping the first human genome cost EUR 2.8 billion in research funds, the cost of a DNA test has dropped to hundred-dollar price brackets.
Today, a blood test can reveal whether a person carries a gene that would increase the likelihood of developing diseases such as gene-related types of cancer. This opens the door to a new school of personal medicine, in which treatments - and even more importantly, preventive measures - can be administered based on an individual's DNA.
When patients develop genetically based cancer, a new generation of treatment such as Ullrich's invention - the anti-cancer drug targeting the HER2 oncogene - achieves far better outcomes. Patients may no longer have to opt for radical preventive surgeries like the one actress Angelina Jolie underwent: aged 37, Jolie chose to have her breasts surgically removed after testing positive for a mutation in the BRCA1 gene, a marker for increased risk of developing cancer of the breast and ovaries.