What is DNA Repair?
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. These mechanisms are essential for maintaining the integrity of genetic information and for preventing mutations that could lead to diseases, including cancer.
How is DNA Repair Linked to Cancer?
Defective DNA repair mechanisms can lead to an accumulation of genetic mutations, which in turn can result in cancer. When the DNA repair processes fail, cells can experience genomic instability, a hallmark of many cancers. Essentially, the inability to correct DNA damage increases the likelihood of mutations that can activate oncogenes or deactivate tumor suppressor genes.
What Causes Defective DNA Repair?
Defective DNA repair can be caused by mutations in genes responsible for the repair processes. For example, mutations in the
BRCA1 and
BRCA2 genes are linked to a significantly higher risk of breast and ovarian cancers due to impaired homologous recombination. Environmental factors such as exposure to UV light, radiation, and certain chemicals can also damage DNA and overwhelm repair mechanisms, leading to defects.
Genomic Instability: Increased mutation rates and chromosomal abnormalities.
Tumorigenesis: Higher likelihood of cells becoming cancerous.
Resistance to Therapy: Tumors with defective repair mechanisms may be more resistant to treatments that induce DNA damage, like chemotherapy and radiation.
Can Defective DNA Repair Be Targeted for Cancer Therapy?
Yes, targeting defective DNA repair mechanisms is a promising approach in cancer therapy. One example is the use of
PARP inhibitors in cancers with BRCA1 or BRCA2 mutations. These inhibitors exploit the defective repair pathways in cancer cells, leading to cell death while sparing normal cells with functional repair mechanisms. This concept is known as synthetic lethality.
New Therapeutic Targets: Identifying additional repair pathways that can be targeted for cancer therapy.
Combination Therapies: Using drugs that target DNA repair in combination with traditional therapies for enhanced efficacy.
Personalized Medicine: Tailoring treatments based on the specific DNA repair defects present in an individual's tumor.
Conclusion
Defective DNA repair plays a critical role in the development and progression of cancer. Understanding the mechanisms behind DNA repair and the consequences of their malfunction can lead to more effective diagnostic tools and targeted therapies, offering hope for improved cancer treatment outcomes.
