Cell cycle involvement in cancer therapy; WEE1 kinase, a potential target as therapeutic strategy

Sajjad Vakili-Samiani, Omid Joodi Khanghah, Elham Gholipour, Fatemeh Najafi, Elham Zeinalzadeh, Parisa Samadi, Parisa Sarvarian, Shiva Pourvahdani, Shohre Karimi Kelaye, Michael R. Hamblin, Abbas Ali Hosseinpour Feizi

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)

Abstract

Mitosis is the process of cell division and is regulated by checkpoints in the cell cycle. G1-S, S, and G2-M are the three main checkpoints that prevent initiation of the next phase of the cell cycle phase until previous phase has completed. DNA damage leads to activation of the G2-M checkpoint, which can trigger a downstream DNA damage response (DDR) pathway to induce cell cycle arrest while the damage is repaired. If the DNA damage cannot be repaired, the replication stress response (RSR) pathway finally leads to cell death by apoptosis, in this case called mitotic catastrophe. Many cancer treatments (chemotherapy and radiotherapy) cause DNA damages based on SSBs (single strand breaks) or DSBs (double strand breaks), which cause cell death through mitotic catastrophe. However, damaged cells can activate WEE1 kinase (as a part of the DDR and RSR pathways), which prevents apoptosis and cell death by inducing cell cycle arrest at G2 phase. Therefore, inhibition of WEE1 kinase could sensitize cancer cells to chemotherapeutic drugs. This review focuses on the role of WEE1 kinase (as a biological macromolecule which has a molecular mass of 96 kDa) in the cell cycle, and its interactions with other regulatory pathways. In addition, we discuss the potential of WEE1 inhibition as a new therapeutic approach in the treatment of various cancers, such as melanoma, breast cancer, pancreatic cancer, cervical cancer, etc.

Original languageEnglish
Article number111776
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume824
DOIs
Publication statusPublished - 1 Jan 2022

Keywords

  • Cancer
  • Cell cycle
  • Checkpoint
  • DNA damage
  • WEE1 kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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