Sutent®: New cancer treatment

Prof. Dr Axel Ullrich and his team at the Max Planck Institute for Biochemistry recognized the need for a multi-specific cancer treatment and developed a concept for interfering with the complex mechanism of tumorigenesis in a targeted way. The company Sugen, founded in 1991 in the US, built on this insight and developed it into a medical application. In 1999 Sugen was bought by Pharmacia, which in turn was acquired by Pfizer in 2003. Subsequently Pfizer pursued the development of Sutent® into a marketable drug. Sutent® was approved by the FDA in January 2006 for the treatment of metastasized gastrointestinal stromal tumours (GIST) and advanced renal cell carcinoma, amongst others. It received EU approval in July 2006.

Sutent® (sutinib) is a drug that interferes with – among other mechanisms of action – the so-called angiogenesis, which plays an important role in tumour growth.

This term is used by biologists to de-scribe the formation of new blood vessels, and these are essential for the growth of tumours. A tumour with a diameter of only 1 mm has reached a critical size at which it is reliant on blood vessels, and can only grow aggressively if new blood vessels grow to supply sufficient oxygen and nutrients.

To accomplish this, tumour cells excrete increased quantities of a growth factor that stimulates endothelial cells (cells that form the inner lining of blood vessels) to divide. This so-called vascular endothelial growth factor (VEGF) binds to certain receptors at the cell surface that act like a switch, initiating particular processes inside the cell, which in turn cause the cells to divide and form new vessels that grow towards the tumour.

Sutent® interferes with this logistical feat by blocking one of the receptors responsible for angiogenesis. This re-ceptor, called Flk-1 or VEGFR-2 (vascular endothelial growth factor receptor 2), is expressed by endothelial cells responsible for the formation of new blood vessels. If it is blocked, no new blood vessels can grow around or into the tumour tissue. As a result, the tumour is unable to grow.

However, Sutent® not only blocks blood vessel formation but also inhibits ad-ditional enzymes within the signalling network of tumour cells relevant for tumour progression.

This simultaneous blocking of several molecular targets essential for tumour growth (so-called multi-specificity) makes Sutent® an efficient therapy in the complex area of tumorigenesis.