Reactivated gene shrinks tumors

P53 plays critical role in the development of many tumors and it is mutated in many cancers. Researchers have identified compounds that restore p53 , but it has not been known whether such activity would actually reverse tumor growth.

In normal cells, p53 controls the cell cycle. In other words, it activates DNA repair mechanisms and prevents cells with damaged DNA from dividing. If DNA damage is irreparable, p53 induces the cell to destroy itself.

When p53 is turned off, cells are much more likely to become cancerous, because they will divide uncontrollably even when DNA is damaged.

In this study, the researchers used engineered mice that had the gene for p53 turned off. But, they also included a genetic “switch” that allowed the researchers to turn p53 back on after tumors developed. Once the switch was activated, p53 appeared in the tumor cells and the majority of the tumors shrank between 40 and 100%.

The researchers looked at two different types of cancer-lymphomas and sarcomas. In lymphomas the cancer cells underwent apoptosis within one or two days of the p53 reactivation.

In contrast, sarcomas did not undergo apoptosis but went into a state of senescence, or no growth. Those tumors took longer to shrink but the senescent tumor cells were eventually cleared away.

The researchers have started trying to understand this difference by identifying other genes that are activated in each type of tumor when p53 turns back on.

The study also revealed that turning on p53 has no damaging effects in normal cells. This means the drugs designed to restore p53 may not have the problem of side effects.

In follow-up studies, the MIT researchers are looking at other types of cancer, such as skin cancer and they plan to see if the same approach will also work for tumor suppressors other than p53.