The body is always making new cells, and sometimes there are errors. Usually, there’s a set of genes that can identify and fix the errors. There are several genes performing this function, and some of them are the POLE and POLD1 genes.
These genes work like spellcheck. When the POLE and POLD1 genes are working, the errors in the DNA get caught and fixed. But when they aren’t working, the “spell check” is broken. This can lead to cancer.
Tumors with POLE/POLD1 mutations often carry a high TMB. Although most are MSS tumors, their high mutational burden can cause them to respond to immunotherapy like MSI-H/dMMR tumors and act like dMMR cancer. This makes them strong targets for immunotherapy.
POLE/POLD1 mutations are seen most commonly in colorectal cancer. Other cancers being studied for POLE/POLD1 mutations include small bowel, gastric, and GEJ cancers. These mutations often occur after birth.
Biomarker testing can be run on tumor or blood samples to determine if a patient has a POLE/POLD1 mutation.
Currently, there are not any FDA-approved therapies approved explicitly for patients with a POLE/POLD1 mutation, however there are many ongoing immunotherapy clinical trials and an approved therapy for patients with TMB-high solid tumors.
Your treatment plan will be unique and dependent on several factors. Ask your doctor how your biomarker test results are informing your treatment plan and if you qualify for any clinical trials.
