The Induction and Repair of DNA Interstrand Crosslinks and Implications in Cancer Chemotherapy

Title:The Induction and Repair of DNA Interstrand Crosslinks and Implications in Cancer Chemotherapy

Volume: 16 Issue: 2

Author(s): Sun Guohui, Zhao Lijiao and Zhong Rugang

Affiliation:

Keywords: Anticancer efficiency, combination chemotherapy, cytotoxicity, DNA interstrand crosslinks, inhibitors, repair mechanism.

Abstract: DNA interstrand crosslinks (ICLs) can be induced by numerous endogenous and exogenous chemical agents with the capacity of covalently binding to two base sites in the two strands of the DNA duplex. A series of normal DNA metabolism processes are affected by ICLs. For example, DNA replication and transcription are interfered during cell division, which is fatal to cell survival. In cancer cells, the induction of ICLs is a significant target for cancer chemotherapies. However, the formation of ICLs in cancer cells can be weakened by the repair mechanisms of DNA damage, which results in resistance to chemotherapies. Therefore, it is necessary to develop highly effective ICL agents for the purpose of achieving good chemotherapeutic effects. Furthermore, the combination of ICL agents with inhibitors of ICL repair is a promising strategy for the clinical treatment of cancer. This review summarizes the development of several types of ICL agents as chemotherapies over the past decades and the mechanisms underlying the repair of DNA ICLs. The potential of ICL repair inhibitors for combination therapy with ICL agents in cancer treatment is also discussed.

Cite this article as:

Guohui Sun, Lijiao Zhao and Rugang Zhong, The Induction and Repair of DNA Interstrand Crosslinks and Implications in Cancer Chemotherapy , Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (2) . https://dx.doi.org/10.2174/1871520615666150824160421