Novel approaches in oncology at AstraZeneca

Advances in the understanding of tumour biology have led to the discovery of new targets that control specific mechanisms essential for tumour spread, growth and survival. In order to fully explore the anticancer potential of these novel approaches, AstraZeneca is developing a broad pipeline of agents targeting a variety of key processes in tumour progression and metastasis. These include two novel antiangiogenic agents, ZD6474 and AZD2171, which are both orally available inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase, AZD2171 being a highly potent inhibitor; ZD6474 also has activity against epidermal growth factor receptor tyrosine kinase. Once-daily administration of these agents has been shown to result in effective inhibition of tumour growth in a broad spectrum of human xenograft models. In contrast to this approach, which prevents new vessel formation, the vascular-targeting agent ZD6126 disrupts the microtubular network responsible for maintaining the shape of immature endothelial cells, thereby selectively destroying the existing tumour vasculature and leading to extensive central necrosis. Other agents with a variety of novel antitumour strategies are also in development. These include AZD0530, an orally available Src kinase inhibitor, and AZD3409, an oral prenyl transferase inhibitor, both of which have potential for broad antitumour activity. In addition, an oral, selective, cyclin-dependent kinase inhibitor (AZD5438). (C) 2003 Elsevier Science Ltd. All rights reserved.