DNA damaging agents and DNA repair: From carcinogenesis to cancer therapy

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Cancer genome instability stems from DNA repair defects, increasing cancer cell susceptibility to DNA targeting agents.
• Double-strand break (DSB) repair pathways, including homologous recombination (HR) and non-homologous end joining (NHEJ), are crucial in this context.
• DNA targeting agents are vital in cancer therapy, often used with targeted therapy and immunotherapy.

Purpose of the Study:

• To review the mechanisms of action of various DNA-targeting agents.
• To explore the modulation of DNA repair pathways to enhance the efficacy of DNA-damaging drugs.
• To discuss DNA-targeting-based therapies, considering risks, resistance, and precision medicine applications.

Main Methods:

• Review of existing literature on DNA targeting agents and DNA repair mechanisms.
• Analysis of the interplay between DNA repair deficiencies and drug efficacy.
• Discussion of therapeutic strategies involving DNA targeting agents and DNA repair modulation.

Main Results:

• DNA targeting agents are classified into non-covalent DNA binding and covalent DNA-reactive types.
• Despite limitations like resistance and secondary carcinogenesis risk, these agents are important in combination therapies.
• Targeting cancer-specific DNA repair failures offers a precise therapeutic approach.

Conclusions:

• DNA targeting drugs are promising therapeutics when applied to cancers with specific DNA repair defects.
• Modulating DNA repair pathways can significantly increase the efficacy of DNA-damaging drugs.
• DNA-targeting therapies hold potential in the precision medicine era, but risks and resistance must be managed.