Advances in DNA damage response inhibitors in colorectal cancer therapy

Abstract

One potential cause of cancer is genomic instability that arises in normal cells due to years of DNA damage in the body. The clinical application of radiotherapy and cytotoxic drugs to treat cancer is based on the principle of damaging the DNA of cancer cells. However, the benefits of these treatments also have negative effects on normal tissue. While there have been notable advancements in molecular-driven therapy and immunotherapy for colorectal cancer (CRC), a considerable portion of patients with advanced CRC do not experience any benefits from these treatments, leading to a poor prognosis. In recent years, targeted therapy aimed at suppressing the DNA damage response (DDR) in cancer cells has emerged as a potential treatment option for CRC patients, offering them more choices for treatment. Currently, the integration of DDR and clinical intervention remains in the exploratory phase. This review primarily elucidates the fundamental principles of DDR inhibitors, provides an overview of their current clinical application status in CRC, and discusses the advancements as well as limitations observed in relevant studies.

Keywords

• DNA damage response
• colorectal cancer
• targeted therapy
• DDR inhibitor