[Cancer and the cell cycle: a current merry-go-round in oncology of clinical relevance]

Abstract

In normal cells the cell cycle, cell proliferation and differentiation are precisely regulated by a variety of different players. These include cyclins, which help to drive cells into mitosis, as well as cyclin-dependent kinase inhibitors which may be viewed as cell cycle brakes. Alterations in such genes and their products are frequent in human cancer. Overexpression of cyclins has been identified in lymphoma and in non-small cell lung cancer. Mutations in cyclin-dependent kinase inhibitors, such as the p16 gene, are particularly frequent in human cancer cell lines. Tumor suppressor genes, including the retinoblastoma gene and the p53 gene, are also crucial in this context, and their inactivation through gene mutations in cancer is frequent. Assessing alterations of genes associated with cell cycle regulation in malignancy or their protein products is of clinical interest. Molecular and immunological techniques to identify such alterations may provide unique markers of prognostic and predictive value in cancer. In addition, the technology is being developed for the treatment of such genetic alteration in cancer cells at the molecular-genetic level. Protocols introducing the wild-type p53 gene in tumors with p53 inactivations are on the way and clinical trials, although very preliminary, seem to be opening up completely new avenues for cancer treatment. Investigating cell cycle alterations in cancer is no longer the exclusive province of experimental research, but has rapidly developed into an area of unique clinical relevance.