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.

Longitudinal analysis of 2293 NSCLC patients: A comprehensive study from the TYROL registry

“…These results are well in line with published data [21]. A number of pathologic and molecular features proved to be prognostic [12,[22][23][24][25][26]. We showed that the patterns of pathological features are the same in young and elderly patients [11].…”

Alantolactone Induces Apoptosis and Cell Cycle Arrest on Lung Squamous Cancer SK‐MES‐1 Cells

“…During the G1 phase, the cell accumulates cyclin D, which forms a complex with CDK4 or CDK6. The complex phosphorylates the retinoblastoma protein (pRb), releasing transcription factors to promote the transcription of the genes required for cell cycle progression . In the present study, alantolactone‐treated cells showed low expression of cyclin D1, cyclin D3, and their partner CDK4 and CDK6; it was suggested that the depletion of cyclin D1, cyclin D3, CDK4, and CDK6 proteins may cause the cell cycle arrest at the G1/G0 phase in alantolactone‐treated cells.…”

Combination of Low Concentration of (−)-Epigallocatechin Gallate (EGCG) and Curcumin Strongly Suppresses the Growth of Non-Small Cell Lung Cancer in Vitro and in Vivo through Causing Cell Cycle Arrest

“…The expression of two main cell cycle related proteins, cyclin B1 and cyclin D1, were investigated by Western blot. Cyclin B1 and cyclin D1 are usually over-expressed in lung cancer cells [16]. Western bolt analysis showed that the expression of cyclin B1 and cyclin D1 (Figure 4A) were strongly repressed at the present of EGCG and curcumin.…”

“…Cell cycle as a therapeutic target is gaining more and more attention [16]. The cell cycle offers a multitude of prognostic, predictive and therapeutic possibilities, though many of which are still in the developing stage [17].…”