A recently published research reports that investigators have developed a novel strategy for reducing the often serious side effects of an important class of modern anticancer drugs — tyrosine kinase inhibitors. The novel drug is supposed to restrict its activity with high selectivity to the malignant tumor.

Severe side effect is one of biggest problems in modern cancer therapy, and ultimately leads to treatment having to be stopped. Targeted cancer drug 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.

Facing such challenge, scientists have been successfully synthesized a new inhibitor that is coordinated to cobalt(III). This leads to initial drug inactivation and, thus, no activity under normal physiological conditions. Only in tumour tissue where low-oxygen conditions unusually 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.

So far, there has been no comparable strategy for reducing the (severe) side effects of tyrosine kinase inhibitors. As a result, there is hope that, in future, the approach presented here will improve the tolerance of the therapy and allow this treatment to benefit patients who have previously had to discontinue it.

Reference:

Tumor-Targeting of EGFR Inhibitors by Hypoxia-Mediated Activation. Angewandte Chemie International Edition, 2014;