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.