A new strategy to reduce the serious side effects of an important class of modern anticancer drugs (tyrosine kinase inhibitors) has been established jointly by an interdisciplinary team of researchers from the University of Vienna (Institute of Inorganic Chemistry) and the Medical University of Vienna (Institute for Cancer Research). The novel drug is supposed to restrict its activity with high selectivity to the malignant tumour.
The occurrence of severe side effects and the development of resistance are two of the biggest problems facing modern cancer therapy. Even the latest, highly targeted cancer drugs such as the tyrosine kinase inhibitors Tarceva or Sutent are affected by these problems, which can ultimately lead to treatment having to be stopped. The effect of this class of inhibitors is based on the specific inhibition of proteins that are over-activated in cancer cells and which drive abnormal cell growth. However, clinical practice has shown that, as a result of the physiological functions of these proteins in healthy tissue, their inhibition can cause severe side effects. As a result, there is an acute need for strategies to restrict the effect of these highly promising new drugs more selectively to the malignant tumour.
The aim of the research was to develop an improved tyrosine kinase inhibitor that is actually inactive and which is only activated selectively in the malignant tissue. This is intended to prevent damage to healthy tissue and therefore minimise side effects for patients. As part of the paper published in the highly respected journal "Angewandte Chemie
[Applied Chemistry], International Edition
", a new inhibitor has been successfully synthesised and coordinated to cobalt(III). This leads to initial drug inactivation and, thus, no activity under normal physiological conditions. Only in tumour tissue where, due to the rapid growth, unusually low-oxygen conditions prevail, the inactive cobalt(III) compound is reduced to cobalt(II) and as a result releases the active drug. The tumour-selective effectiveness of this approach has been demonstrated both in living cells and in tumor-bearing organisms.