The initiation of DNA replication is a crucial decision point in cell proliferation. Chromosomal replication lies at the point of convergence of oncogenic signalling pathways and transduction pathways that trigger proliferation. Unlike these complex redundant pathways, there appears to be only a single mechanism of DNA replication initiation that is conserved in all eukaryotic species studied. This feature makes it a potentially attractive target for both diagnostic and therapeutic intervention. Our investigation of the DNA replication licensing pathway in Homo sapiens is revealing fundamental new insights into the different growth control strategies adopted by self-renewing, stable and permanent tissues and their dysregulation in cancer. The clinical translational studies arising from these scientific investigations are strongly supporting our hypothesis that the replication licensing pathway (RLP), a final and critical step in growth control, is an attractive target for diagnostic exploitation and applicable to a wide range of cancers irrespective of genetic background and histological type. The research programme is divided into seven main projects, which provide the rationale for development of novel diagnostic and therapeutic strategies targeting the DNA replication licensing machinery.