title: Modulation of chemosensitivity through altered expression of cell cycle regulatory genes in cancer.
abstract: Alterations in the expression of genes affecting cell cycle progression occur in all human cancers. These may occur either by overexpression of genes such as cyclin D1, mutation of regulatory genes such as p16, or abrogation of checkpoints following DNA damage as in the cases of mutation or deletion of the p53 gene. Perturbation of the normal functions of these genes has a profound effect on cellular proliferation, differentiation and apoptosis. There is increasing evidence that such alterations may modulate the cellular response to treatment with chemotherapeutic agents. In many cases genetic alterations may induce resistance to drug treatment as in the case of mutations of the p53 gene. However, the deregulated expression of cell cycle genes may also increase sensitivity to treatment by directly altering the expression of the target for chemotherapeutic drugs as in the case of deletion of the retinoblastoma gene. It is crucial to understand the interactions between drug mechanisms of action and the genetic alterations in cancer to exploit potential areas in which the alterations found in tumors may constitute potential vulnerability.
authors.affiliation: Department of Clinical Oncology, Royal Free Hospital Medical School, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hochhauser
mesh_terms: D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000502:physiology; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator; D018816:Genes, cdc; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins