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Defects in G1-S cell cycle control in head and neck cancer: a review
Rob J A M Michalides1, Michiel van de Brekel, Fons Balm
1Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands. rmichal@nki.nl
Abstract:
Tumors gradually develop as a result of a multistep acquisition of genetic alterations and ultimately emerge as selfish, intruding and metastatic cells. The genetic defects associated with the process of tumor progression affect control of proliferation, programmed cell death, cell aging, angiogenesis, escape from immune control and metastasis. Fundamental cancer research over the last thirty years has revealed a multitude of genetic alterations which specify more or less separate steps in tumor development and which are collectively responsible for the process of tumor progression. The genes affected play in normal cells a crucial role in control over cell duplication and the interaction between cells, and between cells and their direct surrounding. This is illustrated on control during the G1/S phase of the cell cycle by its ultimate regulators: cyclins and cyclin dependent kinases. These proteins not only control the transition through the G1/S phase of the cell cycle, but also serve as mediators of the interaction between cells, and between cells and their surrounding. Defaults in the regulation of these proteins are associated with tumor progression, and, therefore, serve as targets for therapy. Defaults in those genes are found in various tumor types, although some of those prevail in particular tumor types. In this review emphasis is given to the defaults that occur in head and neck cancer.
Insights
Cancer progresses through genetic changes affecting cell growth and spread. Dysregulation of cell cycle proteins like cyclins and cyclin-dependent kinases is key, especially in head and neck cancers, offering therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumorigenesis is a multistep process involving genetic alterations.
- These alterations impact critical cellular functions like proliferation, apoptosis, and metastasis.
- Genes controlling cell cycle and cell interactions are frequently affected.
Purpose of the Study:
- To review genetic alterations in tumor progression.
- To highlight the role of cell cycle regulators (cyclins, CDKs) in cancer.
- To focus on genetic defaults in head and neck cancer.
Main Methods:
- Review of fundamental cancer research over the past 30 years.
- Analysis of genetic defects in tumor progression.
- Emphasis on cell cycle control mechanisms.
Main Results:
- Genetic defects drive tumor progression by affecting proliferation, cell death, and metastasis.
- Cyclins and cyclin-dependent kinases are crucial regulators of the cell cycle (G1/S phase) and cell interactions.
- Dysregulation of these proteins is linked to tumor progression and is observed across various cancer types.
Conclusions:
- Genetic alterations are fundamental to tumor development and progression.
- Cell cycle regulators like cyclins and CDKs are critical targets for cancer therapy.
- Specific genetic defaults, particularly in cell cycle regulation, are prevalent in head and neck cancers.