1. Cancer takes many paths through G1/S.
- Author
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Knudsen, Erik S., Witkiewicz, Agnieszka K., and Rubin, Seth M.
- Subjects
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MAMMALIAN cell cycle , *CYCLIN-dependent kinase inhibitors , *CELL cycle , *CYTOLOGY , *CYCLIN-dependent kinases - Abstract
The consensus linear view of G1/S regulation has served the research community for many years. Recent data indicate considerable heterogeneity in cancer cycles as controlled by distinct cyclin-dependent kinase (CDK) and cyclin complexes. Adaptation and unexpected dependencies reveal emerging themes that support a malleable model for cancer cell division. The growing complexity of the cell cycle offers challenges and opportunities in rationally targeting proliferative control. In the commonly accepted paradigm for control of the mammalian cell cycle, sequential cyclin-dependent kinase (CDK) and cyclin activities drive the orderly transition from G1 to S phase. However, recent studies using different technological approaches and examining a broad range of cancer cell types are challenging this established paradigm. An alternative model is evolving in which cell cycles utilize different drivers and take different trajectories through the G1/S transition. We are discovering that cancer cells in particular can adapt their drivers and trajectories, which has important implications for antiproliferative therapies. These studies have helped to refine an understanding of how CDK inhibition impinges on proliferation and have significance for understanding fundamental features of cell biology and cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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