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Updated: May 3, 2026
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Nucleotide metabolism, oncogene-induced senescence and cancer
Katherine M Aird1, Rugang Zhang1
1Gene Expression and Regulation Program, The Wistar Institute Cancer Center, The Wistar Institute, Philadelphia, PA 19104, United States.
Abstract:
Senescence is defined as a stable cell growth arrest. Oncogene-induced senescence (OIS) occurs when an activated oncogene is expressed in a normal cell. OIS acts as a bona fide tumor suppressor mechanism by driving stable growth arrest of cancer progenitor cells harboring the initial oncogenic hit. OIS is often characterized by aberrant DNA replication and the associated DNA damage response. Nucleotides, in particular deoxyribonucleotide triphosphates (dNTPs), are necessary for both DNA replication and repair. Imbalanced dNTP pools play a role in a number of human diseases, including during the early stages of cancer development. This review will highlight what is currently known about the role of decreased nucleotide metabolism in OIS, how nucleotide metabolism leads to transformation and tumor progression, and how this pathway can be targeted as a cancer therapeutic by inducing senescence of cancer cells.
Insights
Oncogene-induced senescence (OIS) halts cancer cell growth by impacting DNA replication. Targeting nucleotide metabolism may offer new cancer therapies by inducing this tumor-suppressing senescence.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Biology
Background:
- Senescence is a stable cell growth arrest mechanism.
- Oncogene-induced senescence (OIS) acts as a tumor suppressor by arresting cancer progenitor cells.
- OIS is linked to DNA replication errors and DNA damage response.
Purpose of the Study:
- Review the role of decreased nucleotide metabolism in OIS.
- Explore how nucleotide metabolism contributes to cancer transformation and progression.
- Discuss targeting nucleotide metabolism for cancer therapy via senescence induction.
Main Methods:
- Literature review of studies on OIS and nucleotide metabolism.
- Analysis of the relationship between nucleotide pools and DNA replication/repair.
- Examination of therapeutic strategies targeting nucleotide metabolism in cancer.
Main Results:
- Decreased nucleotide metabolism is implicated in OIS.
- Imbalanced nucleotide pools are associated with early cancer development.
- Nucleotide metabolism pathways are crucial in OIS and cancer progression.
Conclusions:
- Understanding nucleotide metabolism in OIS is key to cancer research.
- Targeting nucleotide metabolism offers a promising therapeutic avenue for cancer treatment.
- Inducing senescence through nucleotide metabolism modulation could be a novel cancer therapy.
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