DNA Damage and Its Role in Cancer Therapeutics

Abstract

DNA damage is a double-edged sword in cancer cells. On the one hand, DNA damage exacerbates gene mutation frequency and cancer risk. Mutations in key DNA repair genes, such as breast cancer 1 (BRCA1) and/or breast cancer 2 (BRCA2), induce genomic instability and promote tumorigenesis. On the other hand, the induction of DNA damage using chemical reagents or radiation kills cancer cells effectively. Cancer-burdening mutations in key DNA repair-related genes imply relatively high sensitivity to chemotherapy or radiotherapy because of reduced DNA repair efficiency. Therefore, designing specific inhibitors targeting key enzymes in the DNA repair pathway is an effective way to induce synthetic lethality with chemotherapy or radiotherapy in cancer therapeutics. This study reviews the general pathways involved in DNA repair in cancer cells and the potential proteins that could be targeted for cancer therapeutics.

Keywords: DNA damage; cancer therapeutics; mutations.

Figure 1

Types of DNA damage and their repair systems. Exogenous or endogenous insults cause strand breaks and base modification and mutation, and activate specific repair pathways corresponding to the types of DNA damage.

Figure 2

The DNA damage response is responsible for determining the cell’s future. DNA damage sensors recognize damage sites, transmit signals to related DNA damage repair systems, and determine whether the cell undergoes DNA damage repair, cell cycle arrest, or cell death. Any fault in this process could lead to genomic instability and cancer development.