Targeting Cell Cycle to Suppress Cancer Aggressiveness

Abstract

Background: Failure of cell division control due to mutations leading to inactivation or over activation of regulatory proteins is the leading cause of cancer development. Several mitogens and growth factors have been found to regulate cancer cell cycle progression. However, all signalling pathways converge to the cell cycle machinery and thus disruption of cell cycle control offers an attractive therapeutic target for the treatment of cancer. Method: We undertook a comprehensive search of bibliographic databases through PubMed and selected the most relevant and appropriate peer-reviewed research articles. Results: There has been a breakthrough in identification of the cell cycle regulatory molecules and elucidation of their roles in subtle adjustment of the balance between proliferation and apoptosis of cancer cells. This review will shed light on the current understanding of the regulation of the cell cycle pathway links and the feasibility of targeting cell cycle for fighting metastatic cancer. Conclusion: There are cross-talks among the diverse neoplastic cell types acting together on cell cycle to ensure survival, growth and metastasis, by inhibiting apoptosis, promoting angiogenesis, and avoiding immune system. Approaches should be undertaken to synergistically block the activation of the interconnected pathways for effective cancer therapy. Keywords: Cancer, drug targets, cell cycle, metabolic reprogramming, oxidative stress, immunomodulatory microRNAs, extraribosomal functions, CDK, cyclins, genomic instability, check points, p53, therapeutics.