**6.2 Targets for cancer therapy**

PARP1 inhibitors could act as therapeutics for cancer in BRCAness (**Table 2**). Certain therapeutic strategy involves the use of DNA ligase as targets [106]. In BCR-ABL-positive CML it is treated with tyrosine kinase inhibitor Imatinib, this strategy immense hope for targeting A-NHEJ factors for therapeutics. Tobin et al. reported that BCR-ABL-positive CML resistant to Imatinib were sensitive to combinational treatment of Ligase and PARP inhibitors which correlates with hyperactive A-NHEJ [109]. This therapy was effective in therapy resistant breast cancer cell lines as it became


**111**

*Recent Perspectives in Radiation-Mediated DNA Damage and Repair: Role of NHEJ…*

novel therapeutic strategies for AML associated with FLT3 mutations [105].

sensitive to DNA ligase and PARP inhibitors [107]. Many PARP inhibitors obstruct DNA replication by trapping PARP [108]. Lig3α or PARP inhibitors are also included in

Therefore there is an immense possibility of treatment of cancer with A-NHEJ inhibitors which involves tumors with increased A-NHEJ. And it will be interesting to see if there is possibility of protecting an organism from carcinogenesis by limit-

Radiation and other assaults that cause DNA damage leading to double strand break are dealt by the mammalian system by relying on tightly regulated repair pathways that are end-joining or recombination-based repair pathways. These are highly regulated repair pathways and results in accurate restoration of the genome. Error prone double strand break repair is still prevalent despite of its mutagenic potential. We must also understand that it is not simply a backup mechanism that comes into play when accurate repair pathway is not possible. The various factors that regulate it are cell cycle stage, local sequence context (homology), and genome structure. So the error prone repair pathway is also very important as it prevents major genome catastrophe. Detailed survey of literature puts forward the fact that error prone pathway paves way for genome evolution in somatic tissues in context of cancer. It is apparent that clear understanding of how A-NHEJ operates and is regulated inside the cell after double strand break will have important therapeutic

We would like to thank all researchers for their contribution in the field of radiation and sharing the final outcome of their hard work in this field with entire world.

*DOI: http://dx.doi.org/10.5772/intechopen.96374*

implication in context of cancer treatment and cure.

The authors declare there are no conflicts of interest.

ing the function of A-NHEJ.

**7. Conclusion**

**Acknowledgements**

**Conflicts of interest**

#### **Table 2.**

*Disease, impaired repair pathway along with their therapeutic targets.*

*Recent Perspectives in Radiation-Mediated DNA Damage and Repair: Role of NHEJ… DOI: http://dx.doi.org/10.5772/intechopen.96374*

sensitive to DNA ligase and PARP inhibitors [107]. Many PARP inhibitors obstruct DNA replication by trapping PARP [108]. Lig3α or PARP inhibitors are also included in novel therapeutic strategies for AML associated with FLT3 mutations [105].

Therefore there is an immense possibility of treatment of cancer with A-NHEJ inhibitors which involves tumors with increased A-NHEJ. And it will be interesting to see if there is possibility of protecting an organism from carcinogenesis by limiting the function of A-NHEJ.
