© 2004 European Society for Medical Oncology
Signal transduction blockade and cancer: combination therapy or multi-targeted inhibitors?
1 Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford 2 Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow, UK
* Email: david.kerr@clinpharm.ox.ac.uk
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The huge amount of research effort that has gone into understanding the molecular and cell biological processes that give rise to cancer has provided a wealth of information on the critical mechanisms that allow a normal cell to acquire the traits of a tumour cell. This information has defined some of the key regulatory proteins and pathways that come under aberrant control in cancer, and which in turn are responsible for the abnormal growth. From the clinical perspective, therapeutic approaches that correct this aberrant activity could reinstate normal growth or delay the excessive proliferation of tumour cells.
The combined approaches of molecular biology, genomics and structural biology have yielded an increasingly large number of druggable protein targets that continue to be exploited in the drive to develop novel mechanism-based cancer therapeutics, which are expected to exhibit improved efficacy over many of the existing cytotoxic cancer drugs. Currently, it is estimated
Combination therapy with kinase inhibitors
A new trial design paradigm
A randomised phase II, leading to phase III trial
Multi-target kinase inhibitors
Conclusions and perspectives
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