How Breast Cancer Medications Target Genomic Damage in Tumors

Breast cancer research has historically focused on genetic mutations, especially those inherited within families. The discovery of mutations in BRCA genes has been pivotal, revealing that these genetic alterations significantly elevate the risk of not only breast cancer but also other cancers such as ovarian, pancreatic, and prostate. These mutations impair the cell's ability to repair DNA, thereby increasing the likelihood of tumor development.

Interestingly, these same mutations also render cancer cells more vulnerable to certain therapies that target DNA damage. Drugs like PARP inhibitors exploit this weakness by further hindering DNA repair mechanisms, which can lead to cancer cell death. However, the effectiveness of such treatments is often hindered by the tumor's ability to develop resistance.

Recent findings published in the journal Genes & Development by Alessandro Vindigni and colleagues have shed light on how these drugs work at a molecular level. The study demonstrates that PARP inhibitors induce large DNA fractures in tumor cells, creating single-stranded DNA gaps that are crucial for cell survival. These gaps are normally repaired swiftly, but in BRCA-mutant tumors, specialized enzymes called nucleases exacerbate the damage by enlarging these gaps.

This amplified damage overwhelms the cancer cells’ repair capacity, leading to cell death. Understanding this process opens new avenues for enhancing the efficacy of PARP inhibitors. By boosting the activity of these nucleases, it may be possible to make existing therapies more effective, potentially overcoming resistance and improving outcomes for patients with BRCA-mutant breast cancers.

The study underscores the importance of targeting DNA repair pathways in cancer therapy and highlights potential strategies to maximize the damage inflicted on tumor cells, thereby increasing treatment success. This insight provides hope for developing more durable and effective treatments for breast cancer patients with genetic vulnerabilities.

Source: https://medicalxpress.com/news/2025-08-breast-cancer-drugs-exploit-genomic.html