Inhibitors of signal transduction protein kinases as targets for cancer therapy.

Abstract

Cancer development requires that tumour cells attain several capabilities, including increased replicative potentials, anchorage and growth-factor independency, evasion of apoptosis, angiogenesis and metastasis. Many of these processes involve the actions of protein kinases, which have emerged as key regulators of all aspects of neoplasia. Perturbed protein kinase activity is repeatedly found to be associated with human malignancies, making these proteins attractive targets for anti-cancer therapy. The last decade has witnessed an exponential increase in the development of specific small protein kinase inhibitors. Many of them are in clinical trials in patients with different types of cancer and some are successfully used in clinic. This review describes different approaches that are currently applied to develop such specific protein kinase inhibitors and provides an overview of protein kinase inhibitors that are currently in clinical trials or are administered in the clinic. Focus is directed on inhibitors against receptor tyrosine kinases and protein kinases participating in the signalling cascades.