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Current concepts in neuro-oncology: the cell cycle--a review
1Brain Tumor Research Laboratory, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Neurosurgery
|May 1, 1997
Summary
Human malignant brain tumors exhibit uncontrolled cell proliferation due to cell cycle disruptions. Understanding these cell cycle regulators offers potential therapeutic strategies for astrocytoma.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Uncontrolled cellular proliferation is a hallmark of human malignant brain tumors.
- Cancer cells evade normal cell cycle controls due to altered genetic codes.
- Advances in molecular biology have identified critical pathways disturbed in cancer cells.
Purpose of the Study:
- To review the normal cell cycle and its disturbances in cancer cells.
- To examine alterations in cell cycle gene expression in human brain tumors.
- To discuss derangements in positive and negative cell cycle regulators in brain neoplasms.
Main Methods:
- Review of current knowledge on normal cell cycle regulation.
- Analysis of molecular biology findings related to cancer cell cycling.
- Examination of studies on cell cycle gene expression in human brain tumors.
Main Results:
- Cell cycle progression is controlled by cyclin-dependent kinases (CDKs) and cyclins.
- Phosphorylation of the retinoblastoma protein by cyclin-CDK complexes affects cell proliferation.
- CDK inhibitors modulate cyclin-CDK activity and are candidate tumor suppressor genes.
- Cancer cells often exhibit abrogated cell cycle checkpoints due to aberrant regulators.
Conclusions:
- Understanding cell cycle dysregulation in brain tumors is crucial.
- Aberrant expression of positive regulators (cyclins, CDKs) or loss of negative regulators (e.g., p53, p16ink4A, retinoblastoma protein) contributes to cancer.
- Knowledge of molecular cell cycle events may lead to new therapeutic approaches for astrocytoma proliferation.
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