Within our bodies’ cells, a network called DNA damage response (DDR) stays on the lookout for DNA breaks that need to be repaired. One of the specialized groups in this area is called homologous recombination repair (HRR), which involves a set of proteins that work together to fix serious double-strand DNA breaks.
There are several key HRR genes: BRCA1, BRCA2, ATM, CHEK2, RAD51C, BRIP1, BARD1, FANCA, PALB2, etc.
When these genes mutate, it increases the risk of certain cancers because dangerous DNA breaks cannot be repaired. These mutations can be inherited, or they can occur sometime after birth. When HRR mutations form and are found in cancer, they may become a target for a targeted therapy called a “PARP” inhibitor.
Homologous recombination deficiency (HRD) can be assessed when tumors show HRR dysfunction. HRD status (for example, HRD-positive) is a biomarker used in many cancer types. Some biomarker reports will indicate HRD status, and others may outline if a specific HRR gene has a variant or mutation, for example a BRCA1 mutation.
Biomarker testing on tumor tissue can determine HRD status. Genetic testing through blood or saliva can also determine if there’s a mutation in an HRR gene.
Pancreatic cancers with an inherited BRCA mutation (in advanced, specific situations)
There are several promising clinical trials happening for other GI cancer types with HRR gene mutations.
Ask your doctor how your biomarker test results are informing your treatment plan and if you qualify for any clinical trials.
