Abstract

Keywords

۱٫ Introduction

۲٫ DNA damage response

۳٫ DDR and radiotherapy failure

۴٫ DDR inhibitors decrease radio-resistance

۵٫ DDR roles in chemotherapy failure

۶٫ DDR inhibitors decrease chemo-resistance

۷٫ Conclusions

Funding

Availability of data and material

Ethics approval and consent to participate

Consent for publication

Declaration of Competing Interest

Acknowledgements

References

Abstract

Up to now, many improvements have been made in providing more therapeutic strategies for cancer patients. The lack of susceptibility to common therapies like chemo- and radio-therapy is one of the reasons why we need more methods in the field of cancer therapy. DNA damage response (DDR) is a set of mechanisms which identifies DNA lesions and triggers the repair process for restoring DNA after causing an arrest in the cell cycle. The ability of DDR in maintaining the genome stability and integrity can be favorable to cancerous cells which are exposed to radiation therapy or are treated with chemotherapeutic agents. When DDR mechanisms are error-free in cancer cells, they can escape the expected cellular death and display resistance to treatment. In this regard, targeting different components of DDR can help to increase the susceptibility of advanced tumors to chemo- and radio-therapy.

۱٫ Introduction

DNA-damaging agents originating whether from endogenous or exogenous resources are known to threat the viability of every cell of our body [1]. Besides to the cellular issues arising from the great number of mutations and genome instability, the lack of proper responses can establish generations of these defective cells and put our whole body in danger [1]. DNA damage response or DDR is a precise mechanism which contains sensing the lesions, establishing signals, and finally initiating repair processes by the means of these signals [2]. During DDR, cell cycle is also affected by the mediators of DDR and is temporarily stopped in order to inhibit the replication of a defective DNA [3]. In some cases, DNA deteriorations are irreparable and thus, cell death is the only option on the table [3].

In addition to normal cells, cancerous cells are also able to use the same mechanisms for their chemotherapy- and/or radiotherapy-induced damaged DNA. Until DDR is working properly in a cancerous cell, DNA damages would not lead to cell death and thus, treatment would not be considered successful [1]. This means that despite all the advantageous impacts of DDR, it stands in the way of overcoming a great challenge in cancer therapy: resistance to our common methods, chemo- and radio-therapy. Recently, a great number of researchers have worked on targeting distinct components of DDR for enhancing the efficacy of cytotoxic treatments [4]. In this paper, we review the process of DDR briefly and explain the role of its key players in decreasing the susceptibility of cancer cells to common therapeutic procedures. Additionally, the usage of DDR inhibitors on different types of cancer would be discussed for giving an insight for the treatment of advanced stages of this lethal disease.