Selective anticancer activity of a hexapeptide with sequence homology to a non-kinase domain of Cyclin Dependent Kinase 4.

Background: Cyclin-dependent kinases 2, 4 and 6 (Cdk2, Cdk4, Cdk6) are closely structurally homologous proteins which are classically understood to control the transition from the G1 to the S-phases of the cell cycle by combining with their appropriate cyclin D or cyclin E partners to form kinase-active holoenzymes. Deregulation of Cdk4 is widespread in human cancer, CDK4 gene knockout is highly protective against chemical and oncogene-mediated epithelial carcinogenesis, despite the continued presence of CDK2 and CDK6; and overexpresssion of Cdk4 promotes skin carcinogenesis. Surprisingly, however, Cdk4 kinase inhibitors have not yet fulfilled their expectation as 'blockbuster' anticancer agents.

Technological challenges of theranostics in oncology.

Background: Although the term theranostics has been coined only fairly recently, attempts to relate the level of biomarkers to therapeutic response in the oncology clinic go back several decades. After a long period in which a limited number of individual theranostic molecular biomarkers gained general clinical acceptance, extremely powerful genomic and proteomic technologies have now emerged.

Methods: These technologies, reviewed here, promise a potential revolution in our ability to predict therapeutic response in cancer, and by so doing, guide new anticancer drugs more successfully into clinical oncology practice.

Spontaneous regression of human cancer cells in vitro: potential role of disruption of Cdk1/Cdk4 co-expression.

Background: Although well-acknowledged in vivo, spontaneous death of cancer cells in vitro is less widely appreciated.

Materials And Methods: Colony formation was studied in untreated control plates of standard clonogenic assays and measurements of actual and potential doubling times performed in asynchronous cultures of human cancer cells lines. Western blotting of lung large cell carcinoma, COR-L23 cells actively undergoing spontaneous cell death was also carried out.

Dynamic heterogeneity of proteomic expression in human cancer cells does not affect Cdk1/Cdk4 co-expression.

Tumour heterogeneity is becoming increasingly important as an obstacle to genomic and proteomic technologies designed to improve the diagnosis and treatment of human cancer. In a panel of 19 human in-vitro cancer cell lines, we show marked heterogeneity of proteomic expression of key genes responsible for the control of cell division and death. Patterns of expression of these proteins were unique for each cell line.