Presence of Mutated Gene Influences Chemotherapy Efficacy

Study finds mutation of TP53 gene impacts effect of chemotherapy in colon cancer patients.

Whether the TP53 gene is mutated or not has a significant impact on a cancer patient’s overall survival, a recent study found.

Over the last 15 years, the p53 research group at MedUni Vienna has studied over 1000 patients with different types of cancer. Researchers found that chemotherapy treatments were only effective if the TP53 gene was not mutated within the tumor.

Those with a normal TP53 gene were found to live significantly longer than those with the mutated gene.

“The theoretical possibility that a single gene could be the key in the battle against cancer gave rise to a lot of hype about this gene 25 years ago and this still continues today,” said lead researcher Daniela Kandioler.

The impact of the results from the MARK53 analysis on the efficacy of common chemotherapy using fluorouracil (5-FU) was able to be demonstrated in a large scale clinical trial.

The study enrolled 400 patients with colorectal cancer and found that when the MARK53 result was normal, patients survived significantly longer than expected. If the MARK53 result was mutated, patient survival was shorter than expected.

“It was also important to discover that the marker is exclusively predictive, that means the marker can predict the effect of a therapy,” Kandioler said. “If no treatment — or ineffective treatment – is being given, no effect will be predicted.”

The act of destroying the DNA of cancer cells is the most powerful activator of the TP53 gene, which codes for a protein weighing 53 kilodaltons.

The TP53 gene is also referred to as the “Guardian of the Genome,” because of its role ensuring that human genetic information is not damaged.

If irreparable DNA damage is detected, p53 sends the cell into apoptosis. However, this can only happen if the TP53 gene is not mutated. In cancer patients, the TP53 gene is often mutated and occurs with varying frequency in almost all types of cancer.

A general rule is that every second tumor most likely carries a mutated TP53 gene.

“The clinical use of the p53 gene as a biomarker would be the most effective method we currently have to increase the efficiency of cancer treatment and, at the same time, reduce the risk to patients — because it is crucial to choose the right chemotherapy for the right patient,” Kandioler said.