Boehringer Ingelheim and the search for new targeted cancer treatments
Summary
Boehringer Ingelheim and the search for new targeted cancer treatments
Founded in 1885, Boehringer Ingelheim is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim am Rhein, Germany, it is a family-owned, globally operating research-driven group of companies committed to the goal of serving mankind through research into diseases and the development of new treatment options of high therapeutic value for human and veterinary medicine.
 | The Boehringer Ingelheim group, with 137 subsidiaries in 47 countries across the world and a total of approximately 38,500 employees, reported net sales of almost 10.6 billion Euros in 2006. With its activities focused on Human Pharmaceuticals and Animal Health, Boehringer Ingelheim demonstrates a clear commitment to improving the health of generations to come, investing 1.6 billion Euros in research |
Leaders in the areas of respiratory medicine, with its blockbuster product Spiriva®, Boehringer Ingelheim is also making significant contributions to research in cardiovascular medicine, neuroscience and urology, as well as in virology, women’s health and immunology.
Cancer is a major public health problem and despite considerable advances remains an area of significant unmet medical need. As a research-driven pharmaceutical group of companies, Boehringer Ingelheim has a long-term commitment to deliver tomorrow’s cancer therapies by discovering and developing novel treatment options that combine ground-breaking science with high therapeutic value for patients, physicians and healthcare providers.
 | More than 400 employees around the world are dedicated to the discovery and development of new cancer treatments: 200 in Vienna, Austria at the dedicated Boehringer Ingelheim cancer research centre and more than 200 across the globe associated with oncology research and development.
Their efforts, combined with close collaboration with the Research Institute of Molecular Pathology (IMP) in Austria and the expertise of many leading experts in all areas of cancer research and medicine, are focused on developing a broad range of breakthrough products to combat cancer. |
Boehringer Ingelheim is committed to the clinical development of pioneering treatments for cancer through an extensive and diverse global study programme involving investigators and patients from around the world. This is supported by a significant financial investment from Boehringer Ingelheim, with the aim of developing treatments that will offer important advances and make a real difference to the lives of patients and their families.
 | Boehringer Ingelheim is using its significant resources to actively develop targeted therapies – biologicals and small molecules – in areas of unmet medical need including both solid and haematological cancers. Using technological advances and breakthrough science, the search for new cancer treatments is currently focused on three areas: |
- Angiogenesis inhibitors
- Signal-transduction inhibitors
- Cell-cycle kinase inhibitors
Angiogenesis Inhibitors
Angiogenesis, or the growth of new blood vessels, is an important natural process occurring in the body, both in health and in disease. In a healthy body, angiogenesis occurs in wound healing and to restore blood flow to damaged tissues. However, excessive angiogenesis occurs in diseases such as cancer, in which the new blood vessels feed diseased tissues with oxygen and nutrients, encouraging tumour growth and allowing tumour cells to escape into the circulation, leading to growth of secondary tumours or metastases.
Angiogenesis is regulated by both activator and inhibitor molecules.
Many tumours release naturally occurring activators of angiogenesis, such as vascular endothelial growth factor (VEGF). Inhibitors of angiogenesis are also produced and there is normally a balance between inhibition and activation. There are many mechanisms involved in this process, which offer several targets for therapeutic intervention.
Boehringer Ingelheim is developing new treatments that target and inhibit the key biological pathways involved in stimulating angiogenesis, thereby preventing growth and spread of the tumour. BIBF 1120 is a triple angiokinase inhibitor that simultaneously acts on vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR). As these growth factors and receptors play an important role in angiogenesis, inhibition of them may play a critical role in the prevention of tumour growth and spread. Currently in advanced Phase II development, BIBF 1120 is an orally administered small molecule.
As angiogenesis plays a pivotal role in the growth of all solid tumours, BIBF 1120 is currently being investigated in a number of indications, including advanced non-small cell lung cancer (NSCLC), colon, prostate and ovarian cancers.
Signal-Transduction Inhibitors
Cell proliferation, differentiation and programmed cell death (apoptosis) are tightly regulated in healthy tissues by a variety of external signals working via receptors that activate intracellular signal-transduction pathways. Cancer cells acquire genetic mutations that deregulate these signal-transduction pathways, resulting in malignant cells that proliferate uncontrollably and do not respond to the signals that normally activate apoptosis.
This disruption stems from the over-activity of multiple signalling pathways – for example, the epidermal growth-factor receptor (EGFR) and human epithelial receptor 2 (HER2) signalling. Over-expression of EGFR and HER2 may be associated with poor prognosis and advanced-stage cancers. Inhibition of one receptor type alone may not be sufficient for optimal inhibition of tumour cell proliferation and survival. Dual EGFR and HER2 inhibition may provide a complete block of EGFR/HER family signalling.
BIBW 2992*, a compound of Boehringer Ingelheim research that is currently being investigated in Phase II studies, is a novel representative of the second generation of tyrosine kinsase inhibitors. This new compound is a potent and irreversible inhibitor of both the EGFR and HER2 kinases and is being investigated for oral administration in various solid tumours including breast, colorectal, prostate and lung cancer.
Cell-Cycle Kinase Inhibitors
The cell cycle describes the series of events between one cell division and the next. It is the process by which a single cell develops into a mature organism and the process by which hair, skin, blood cells and some internal organs are renewed. Disruption of this process is a fundamental feature of cancer.
The mitotic spindle is vital for successful cell division. Cell-cycle kinases, such as polo-like kinase 1 (Plk1), are proteins that influence the processes of cell division, such as formation of the mitotic spindle.
Over-expression of Plk1 is associated with aggressiveness and a poor prognosis in many cancers. Inhibition of Plk1 induces mitotic arrest and apoptosis in vivo tumour models, resulting in growth inhibition and tumour regression. Plk1 may therefore be a suitable target for cancer therapy.
Boehringer Ingelheim is exploring the potential to arrest cancer cell proliferation by developing compounds that target cell-cycle kinases. The Company’s development in this area focuses on novel, highly selective, potent and potentially first-in-class inhibitors of Plk1, which may provide the specificity of a targeted chemotherapy compound with the efficacy of a broad-spectrum cytotoxic agent. Potentially suitable for the treatment of various cancer types, it is thought to be the most advanced Plk1 inhibitor in clinical development.
