Cells throughout the body carry a gene called TP53. This gene makes a protein called p53. The job of this protein is to guard the body’s DNA and prevent cancer. It does this by identifying and stopping cancer cells when they start. P53 can activate certain cancer-fighting genes. It can also program a bad cell to die. The protein is nicknamed “guardian of the genome,” and it’s called a tumor suppressor protein.
In about 50% of cancers, there’s a mutation in the TP53 gene, called TP53-mutated. TP53 is the most frequently mutated gene amongst all cancer types.
This mutation can be inherited (found in a syndrome called Li-Fraumeni (LFS)), but usually in GI cancers, the mutation is caused by external factors like being exposed to carcinogens (smoking, UV rays, certain chemicals, etc.), prior cancer treatment, or certain viruses (like HPV). Sometimes, there is no known cause for why TP53 mutates.
Other times, there are additional genes that are responsible for TP53’s malfunction. For example, the protein MDM2 can bind to p53 and inactivate its cancer-fighting role. This is seen in the biliary tract cancers (cholangiocarcinoma and gallbladder) as well as gastric cancer.
When TP53 mutates, the p53 protein malfunctions and it can’t guard the genome. This can lead to an environment where cancer forms and spreads because the protein that usually stops damaged cells from multiplying is broken. Cancers with a mutation in TP53 are often more aggressive and harder to treat.
In some cancers, knowing if a patient is TP53-mutant or not (normal genes are also called wild-type), may help doctors determine if a patient will have a better response to standard chemotherapy. Those with mutated genes may not respond as well as those without the mutation.
A high percentage of esophageal, colon, rectal, and pancreatic cancers have a TP53 mutation.
Biomarker testing can be run on tumor or blood samples to determine if there’s a mutation in the TP53 gene. Genetic testing can also determine if there’s a mutation–even if it’s not inherited.
Currently, there are not any FDA-approved therapies for patients with a TP53 mutation, however there are many ongoing clinical trials for TP53-mutant patients. Several are showing promise.
Ask your doctor how your biomarker test results are informing your treatment plan and if you qualify for any clinical trials.
