Spread of Advanced Lung Tumours Slowed Down Through Restoring Gene

Restoring the gene for cancer protein p53 could slow down the spread of advanced lung tumours, reveal cancer biologists, but this may not help in early-stage cancers.

The findings by experts from the Massachusetts Institute of Technology suggested that drugs that restore p53 function could help prevent aggressive lung cancers from metastasising, though they might spare benign tumour cells that could later turn aggressive.

"Even if you clear the malignant cells, you're still left with benign cells harbouring the p53 mutation," said David Feldser, lead author and a postdoctoral fellow at the David H. Koch Institute for Integrative Cancer Research at MIT.

However, such drugs are still worth pursuing because they could prolong the life of the patient, he said.

P53 is known to control the cell cycle, which regulates cell division. In particular, the protein stops a cell from dividing when its DNA is damaged. P53 then activates DNA repair systems, and if the damage proves irreparable, it instructs the cell to commit suicide.

Without p53, cells can continue dividing even after acquiring hazardous mutations. Eventually, after a cell accumulates enough mutations, it becomes cancerous.

The researchers studied mice that were genetically engineered to develop lung tumours shortly after birth.

Those mice also have an inactive form of the p53 gene, but the gene includes a genetic 'switch' that allows the researchers to turn it back on after tumours develop.

At first, the researchers turned on p53 in mice that were four weeks old and had developed tumours known as adenomas, which are benign. To their surprise, restoring p53 had no effect on the tumours.

Then they turned on p53 in another group of tumour-prone mice, but they waited until the mice were 10 weeks old. At this point, their tumours had progressed to adenocarcinomas, a malignant type of cancer. In these mice, turning on p53 cleared the malignant cells, but left behind cells that had not become malignant.

This suggests that the p53 signalling pathway is recruited only when there is a lot of activity from other cancer genes.

In benign tumours, there is not enough activity to engage the p53 system, so restoring it has no effect on those tumours. In the malignant tumour cells, reactivated p53 eliminates cells with too much activity in a signalling pathway involving mitogen-activated protein kinase (MAPK), which is often overactive in cancer cells, leading to uncontrolled growth.

The researchers are now looking for drugs that would reactivate mutant forms of p53, and also plan to study whether tumours that have metastasised would be vulnerable to p53 restoration.

The study is published in the latest issue of Nature.

Source: ANI