DNA damage repair and cancer treatment
Certain genes are important for repairing DNA damage. These genes are sometimes referred to as "DNA damage repair" (DDR) genes. Our animated video below explains how mutations can lead to cancer.
- In a normal cell, a mutation in a DDR gene increase the chance that it will become cancer. This is why an inherited mutation in a gene that repairs DNA damage increases the risk for cancer.
- In a cancer cell, a mutation in a DDR gene can keep it from repairing damage caused by treatment. This means that cancer cells with mutations in these genes may be more sensitive to certain treatments.
Two main types of DNA damage repair genes are linked to increased cancer risk and improved response to certain types of treatment:
Genetic tests can identify people with an inherited mutation in a DDR gene. Biomarker tests can find tumor cells that have difficulty repairing these types of DNA damage.
Homologous Recombination Response (HRR) genes repair a type of DNA damage known as "double-stranded DNA breaks." Cancers with difficulty repairing this type of DNA damage are known as HRD (homologous recombination deficient). Cancers that have difficulty repairing this type of DNA damage may respond better to treatment with a type of targeted therapy known as PARP inhibitors.
- Genetic testing for inherited (germline) mutations may help identify people who would benefit from treatment with a PARP inhibitor. This includes people with advanced breast, ovarian, pancreatic or prostate cancer.
- Tumor testing for acquired (somatic) mutations may help identify people who would benefit from treatment with a PARP inhibitor. This includes people with advanced ovarian or prostate cancer.
- HRD testing is a special type of biomarker test to find tumors that have difficulty repairing double-stranded DNA damage. HRD testing looks for "genomic instability" within tumors, that makes it hard for them to repair DNA damage. Tumors that have this type of genomic instability are sometimes called "HRD-positive." HRD testing can help find ovarian cancers that respond better to PARP inhibitors. HRD testing may also be used to find people who qualify for certain clinical trials.
- HRR testing is a special type of biomarker test to find tumors that have certain mutations that may make them sensitive to PARP inhibitors. HRR testing can help find prostate cancers that respond better to PARP inhibitors. HRR testing may also be used to find people who qualify for certain clinical trials. HRR testing looks for tumor mutations in the following genes:
"Mismatch repair" (MMR) genes repair DNA damage that occurs during cell division. Tumors with mutations in mismatch repair genes are called "mismatch repair deficient" (also called dMMR or MMR-D). These tumors have a cellular abnormality known as Microsatellite Instability or MSI-High. Mutations in the following genes may be associated with dMMR tumors:
Testing tumors for dMMR/MMR-D or MSI-High can be important, because these tumors are more likely to respond to a type of immunotherapy known as immune checkpoint inhibitors.
Some tumor biomarker tests look for gene mutations in cancer cells. These tests differ from genetic tests for inherited cancer risk.
As cells become cancerous, they develop many gene mutations that cause abnormal growth. These gene changes, which occur after you are born and throughout your life—are known as acquired or "somatic" mutations. Acquired mutations are different than inherited mutations, which are passed on from parent to child and are present at birth in every cell.
Tumor biomarker tests can look for mutations in cancer cells. Genetic tests for inherited mutations look at normal cells in blood or saliva to find gene changes that are present from birth, passed from parents to children and are linked to increased risk for hereditary cancer.
Information provided by tumor testing and genetic testing may overlap. When someone with an inherited mutation develops cancer, their cancer cells will likely carry the same mutation. For example, a person born with a BRCA1 mutation will have that mutation in all of their cells. If they develop cancer, their cancer cells will likely also have the same BRCA1 mutation. If a person born with an inherited MSH6 mutation develops colorectal cancer, their cancer cells will have the same mutation and will likely also be MSI-High.
Not all tumor biomarker tests can distinguish inherited mutations from acquired mutations. If your biomarker test shows a mutation, ask your doctor if it may be hereditary and if you should have genetic testing for an inherited mutation.