Investigating families with several members affected by breast cancer has led to the identification of mutations in BRCA genes. Medical professionals have determined that these mutations heighten the likelihood of developing various tumor types, including breast, ovarian, pancreatic, and prostate cancers. While these BRCA mutations escalate cancer risk by hindering DNA repair, they can also render cancer cells more vulnerable to treatments that damage DNA or further disrupt DNA repair — however, the effectiveness of these therapies is frequently hampered by the emergence of resistance, the reasons for which had been unclear to scientists.

Recently, a study published in Genes & Development and spearheaded by Alessandro Vindigni, a professor of medicine in the Division of Oncology at WashU Medicine, has demonstrated how a category of cancer therapies known as PARP inhibitors generates substantial fractures in the DNA of tumor cells. These fractures are characterized by segments of single-stranded DNA, referred to as DNA gaps, which need to be swiftly repaired to guarantee cell survival.

The researchers discovered that certain enzymes, known as nucleases, amplify these gaps in BRCA mutant tumors. This severely weakens the capacity of cancer cells to mend these gaps, ultimately resulting in their death.

The researchers indicated that this newfound understanding opens the door to enhancing the efficacy of PARP inhibitors and restoring the response to these inhibitors by creating strategies to enhance the actions of the enzymes that enlarge the DNA gaps, thereby damaging the DNA molecule beyond repair and improving the therapy’s potential to eradicate cancer cells.

The post How breast cancer drugs exploit genomic fractures in tumors appeared first on The Source.