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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Targeting Poly (ADP) Ribose Polymerase I (PARP-1) and PARP-1 Interacting Proteins for Cancer Treatment

Author(s): Elza T. Sakamoto-Hojo and Adayabalam S. Balajee

Volume 8, Issue 4, 2008

Page: [402 - 416] Pages: 15

DOI: 10.2174/187152008784220302

Price: $65

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Abstract

Cancer is a disease of uncontrolled cellular proliferation. Chemotherapy and radiation therapy are the two main modalities for cancer treatment. However, some cancer types have been found to be refractory to these treatments. Additionally, certain chemicals that are used in clinical trials produce high cytotoxicity as a secondary effect. Hence, current research is focused on finding ways by which cancer cells can be specifically sensitized to apoptotic death with minimal or no secondary effects on normal healthy cells. Since the resistance of cancer cells to DNA damaging agents stems from the modulation of DNA repair pathways, pharmacological inhibition of these pathways has been emerging as an effective tool for cancer treatment. Inhibition of key proteins involved in the molecular cascade of DNA damage detection and repair such as poly (ADP) ribose polymerase I (PARP-1) and its interacting proteins [DNA dependent protein kinase (DNA-PK) and Cockayne syndrome group B (CSB)] has recently proven to be successful for the treatment of various types of cancer cells and tumor xenografts in vitro. This review summarizes some of the recent findings and the potential application of DNA repair inhibitors in cancer treatment.

Keywords: Poly (ADP) ribose polymerase I, DNA-dependent protein kinase, Cockayne syndrome group B gene, nucleotide excision repair, base excision repair, DNA double strand breaks, DNA repair inhibitors and cancer treatment


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