Prognostic and predictive value of cell cycle deregulation in non-small-cell lung cancer

Abstract

Non-small-cell lung cancer (NSCLC) is among the most frequently diagnosed malignancy and a leading cause for cancer mortality worldwide. Despite various efforts, practical prognostic and predictive markers are still few. We review recent findings concerning the cell cycle in NSCLC and discuss prognostic and predictive aspects as well as the challenge of targeted therapeutic approaches. Deregulation of the cell cycle is a common event in NSCLC. Usually, several defects of cell cycle regulation are concomitant and have a cumulative adverse effect on prognosis. Therefore, analysis of a variety of interacting molecules is desirable for adequate deductions. Immunohistochemical interpretations should include the subcellular staining localization, since this can reflect the functional properties of a protein. Overexpression of cyclins, especially D-type cyclins, has repeatedly been associated with poor prognosis in NSCLC. Predictive data is less conclusive; however, loss of the expression of cyclin-dependent kinase inhibitors seems to correlate with sensitivity to antiproliferative drugs. Various inhibitors of Aurora kinases are currently being evaluated regarding their potential as targeted therapies in NSCLC. In conclusion, the cell cycle offers several prognostic, predictive and therapeutic possibilities in NSCLC, many still developmental. Progress in this field has the potential to improve the current scenario for NSCLC patients.