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Article Details


Genomic instability in cancer: molecular mechanisms and therapeutic potentials

Author(s):

Arash Salmaninejad, Khandan Ilkhani, Havva Marzan, Jamshid Gholizadeh Navashenaq, Samira Rahimirad, Fatemeh Radnia, Meysam Yousefi, Zahra Bahmanpour, Sara Azhdari and Amirhossein Sahebkar*  

Abstract:


DNA damage usually happens in all cell types, which may originate from endogenous sources, (i.e., DNA replication errors) or be emanated from radiations or chemicals. These damages range from changes in few nucleotides to large structural abnormalities on chromosomes and, if not repaired, could disturb the cellular homeostasis or cause cell death. DNA repair, as the most significant response to DNA damage, provides biological pathways by which DNA damages are corrected and returned into their natural circumstance. However, aberration in the DNA repair mechanisms may result in genomic and chromosomal instability and the accumulation of mutations. The activation of oncogenes and/or inactivation of tumor suppressor genes are serious consequence of genomic and chromosomal instability and may bring the cells into a cancerous phenotype. Therefore, genomic and chromosomal instability is usually considered as a crucial factor in the carcinogenesis and an important hallmark of various human malignancies. In the present study, we review our current understanding of the most updated mechanisms underlying genomic instability in cancer and discuss about the potential promises of these mechanisms in finding new targets for the treatment of cancer.

Keywords:

Genomic instability; Chromosomal instability; DNA replication; DNA repair; Oncogene; Tumor suppressor gene; Cancer; Molecular mechanisms

Affiliation:

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Department of Pathology and Experimental Animals, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Department of Anatomy and Embryology, School of Medicine, Bam University of Medical Sciences, Bam, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad



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