The Story of TP53

GENE STORY

The Story of TP53

The guardian of the genome keeps cellular DNA in good working order.

TP53 Mutations at a Glance
  • TP53 mutations are implicated in half of all cancers, including lung cancer, breast cancer, bladder cancer, colon cancer, brain cancer, liver cancer, and cancer in other organs.

  • TP53 is known as the “guardian of the genome.” It controls many processes in the cell. It produces a protein that checks DNA before cell division to make sure everything’s correct, and controls the action of some 20 other genes.

  • In healthy tissue, TP53 suppresses the formation of tumors. When TP53 is mutated or absent, cell growth can go out of control, and DNA may quickly accumulate errors, which can lead to cancer.

  • Clinical trials are targeting TP53 with gene therapy. One approach, marketed as Gendicine or Advexin, uses a virus to hack cancer by inserting a healthy TP53 gene. It has shown promising early results in lung cancer and head and neck cancer.

  • Another approach currently in clinical trails uses the virus ONYX-15 to attack cancer with TP53 mutations directly; clinical suggest the virus doesn’t slow cancer, but may make it more susceptible to chemotherapy.

  • TP53 can help define prognosis, although there are not straightforward clinical guidelines. The mutations can be used to figure out where metastasis began, distinguish primary and recurrent tumors, and predict how it will spread.

  • TP53 testing requires a sample of the cancer, ideally taken recently.

Get started and a Cure Forward Clinical Trial Navigator will help you access active clinical trial options.

Cureforward Register Icon
Gene Story Icon

TP53

This gene is also known as:

TP53, P53, BCC7, LFS1, P53 Tumor Suppressor, TRP53

If any gene has a right to be called “the cancer gene,” it’s TP53, which is implicated in a staggering 50 percent of all cancers, including tumors in lung, breast, colon, brain, liver, and other organs. But it’s not quite right to lay the blame for all those illnesses at TP53’s door, because when the gene functions properly, it prevents tumors, rather than causing them.


Dubbed the “guardian of the genome,” TP53 plays important roles in regulating cell division. When those functions get screwed up, cancer can result. It is one of the most-studied genes, with more than 70,000 scientific papers concerning it or the p53 protein it produces published, and 35,000+ different mutations currently logged. TP53 is a gene located on chromosome 17, and each adult has two copies of this gene in every cell nucleus (one from the father, and one from the mother). Although the gene itself is comparatively small – only about 20,000 base pairs long, it’s the big kahuna of genes related to cancer.

In order to understand how TP53 plays a role in the development of cancer, it’s necessary to understand a little about the gene itself and how cell division works.

TP53, short for tumor protein 53, codes for a protein called p53; named, in turn, for its apparent weight of about 53,000 daltons (a unit of measure for protein size), which is actually pretty small as proteins go. P53 controls many processes within a cell. If your cells were an airport, p53 would be the security check, making sure that no one shady gets on board the plane. P53 checks cellular DNA right before cell division occurs, to make sure everything is normal before it is replicated, as well as at other critical points during the process.

If there are errors in cellular DNA, p53 does one of three things at these checkpoints: (1) it pauses the cell replication process until the DNA is repaired, (2) it tells the cell not to divide, and lets the cell live out the rest of its life as-is (3) if the damage is severe, it tells the cell to commit suicide (aka “programmed cell death” or “apoptosis”).


P53 is called a “transcription factor” – it has the power to make certain parts of cellular DNA accessible. Imagine your DNA as a jump rope. If I sit in the middle of the jump rope, you’d only be able to move either end – my posterior would render that center portion of string inaccessible to you. In the same way, p53 regulates the cell cycle by sitting on different parts of the DNA strand. Through these means, it controls the actions of some 20 other genes.

TP53 is a tumor suppressor – when it works properly it is part of the body’s natural defenses against tumors – it puts the brakes on unchecked cell growth. So when it doesn’t work properly, the cell can function like a car with a broken brake – its growth accelerates out of control, causing cancer.

Because TP53 is complex, there are a number of different ways in which it can cause cancer:
• Loss of function mutations. A mutation might produce a p53 protein that is malformed. A malformed protein will sit on the strands of DNA wrong, setting off a chain reaction in which the wrong proteins are activated, leading to cellular chaos, and possibly cancer.
• Dominant negative mutations. A mutation or virus can disable or delete TP53, meaning that p53 doesn’t get produced , and letting all sorts of bad DNA through the checkpoint. Since we all have two copies of TP53, if one goes bad, there is a backup copy in the cell. But some mutations make one copy of TP53 disable the other.
• Gain of function mutations. A mutation can lead TP53 to produce a p53 protein that has extra abilities. The souped-up p53 is more super villain than superhero and can galvanize cellular growth. This sort of p53 mutation is not yet very well understood.

TP53 is implicated in both inherited and sporadic cancer (not inherited, but arising in an individual). All it takes is a couple mutations in a single cell – caused by environmental exposure, radiation, or aging for TP53 to become disabled and play a role in the development of cancer.

In contrast, inherited cancer is cause by a genetic mutation that is passed down from a parent. This genetic mutation is part of a person’s DNA – it exists in every cell of the body. A faulty TP53 gene inherited from a parent causes Li-Fraumeni syndrome, a severe propensity for cancer that is very rare.

The bad news for patients with tumors bearing a TP53 mutation, whether they have sporadic or [factbox target=”fb4″}inherited cancer, is that there is no magic bullet. Depending on the type of cancer a person has, and whether their tumor is missing a TP53 gene or has a mutated one -their cancer may be more receptive to certain treatments such as radiation or specific chemotherapy compounds.


Although gene therapy treatments for cancer are not yet on the market, they are currently in testing. Essentially, cancerous cells with error-containing TP53 genes don’t die off like they should. So why not try to stop the problem at its source? The method used corresponds to the TP53 problem:

• For patients whose tumor has no TP53 gene, researchers are testing an approach where a virus with a healthy TP53 gene is used to insert normal TP53 code into the cancer’s genome, a type of hacking, you might say. In a one-two punch, researchers are also exploring follow-up chemotherapy and radiation, to which cells with the inserted TP53 become more susceptible. This gene therapy approach, known commercially as Gendicine or Advexin, has been in clinical use in China since 2003 and is currently in clinical trials in the US. Early results suggest the approach may be helpful in some cancers, especially lung cancer and head and neck cancer.

• For tumors that have mutated TP53 genes, researchers are exploring the possibility of using viruses like the common cold virus, which are drawn to cells with altered p53 proteins, and ultimately burst them. Clinical trials suggest that this therapy doesn’t work very well to slow cancer, but it can make chemotherapy more effective in a number of cancers. The virus, known as ONYX-15, is currently in clinical trials.

These represent only a few of the cancer-fighting avenues scientists are currently exploring around the p53 protein. Other avenues include using tiny molecules to activate p53 pathways, deactivating p53 pathways in healthy tissue to help reduce the risk of side effects in chemotherapy, and more. For such a tiny gene, TP53 works in complex ways, and it may take another few decades of research until we are able to until we are able to systematically address TP53 mutations to prevent and stop cancers.

© 2017 | Cure Forward. All rights reserved.