Τίτλος:
Targeting DNA damage and repair: Embracing the pharmacological era for successful cancer therapy
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
DNA is under constant assault from genotoxic agents which creates different kinds of DNA damage. The precise replication of the genome and the continuous surveillance of its integrity are critical for survival and the avoidance of carcinogenesis. Cells have evolved an arsenal of repair pathways and cell cycle checkpoints to detect and repair DNA damage. When repair fails, typically cell cycle progression is halted and apoptosis is initiated. Here, we review the different sources and types of DNA damage including DNA replication stress and oxidative stress, the repair pathways that cells utilize to repair damaged DNA, and discuss their biological significance, especially with reference to cancer induction and cancer therapy. We also describe the main methodologies currently used for the detection of DNA damage with their strengths and limitations. We conclude with an outline as to how this information can be used to identify novel pharmacological targets for DNA repair pathways or enhancers of DNA damage to develop improved treatment strategies that will benefit cancer patients. © 2011 Elsevier Inc. All rights reserved.
Συγγραφείς:
Aziz, K.
Nowsheen, S.
Pantelias, G.
Iliakis, G.
Gorgoulis, V.G.
Georgakilas, A.G.
Περιοδικό:
Developmental Pharmacology and Therapeutics
Λέξεις-κλειδιά:
bleomycin; breast cancer resistance protein; carboplatin; cisplatin; DNA base; DNA topoisomerase; doxorubicin; etoposide; free radical; hydrogen peroxide; irinotecan; iron; methotrexate; Mre11 protein; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; platelet derived growth factor receptor; polycyclic hydrocarbon; polydeoxyribonucleotide synthase; pyrimidine; reactive nitrogen species; sunitinib; tar; taxane derivative; temozolomide; topotecan; unindexed drug; vasculotropin receptor; vinyl chloride; XRCC1 protein, anaphase; apoptosis; cancer cell; carcinogenesis; cell cycle checkpoint; cell cycle S phase; cell death; cell phagocytosis; cell respiration; cell stress; chromosome; chromosome aberration; deamination; dietary intake; DNA adduct; DNA alkylation; DNA binding; DNA cleavage; DNA cross linking; DNA damage; DNA end joining repair; DNA methylation; DNA protein complex; DNA repair; DNA replication; DNA strand breakage; DNA transcription; drug resistance; enzyme inhibition; Fenton reaction; gene amplification; gene overexpression; genomic instability; genotoxicity; human; inflammation; ionizing radiation; linear energy transfer; lipid peroxidation; mechanical torsion; mitosis spindle; molecular diagnosis; molecularly targeted therapy; nonhuman; oxidative stress; priority journal; progeny; prognosis; protein phosphorylation; review; signal transduction; single stranded DNA break; smoke; soot; tautomerization; thermal exposure; ultraviolet A radiation; ultraviolet B radiation; virus infection, Animals; Antineoplastic Agents; DNA Damage; DNA Repair; Humans; Neoplasms
DOI:
10.1016/j.pharmthera.2011.11.010
