Dr. Dean Felsher, Associate Professor of Medicine (oncology) and Pathology, says that the surprising possibility that a cell's own natural mechanism for ensuring its mortality may be used to vanquish tumours opens the door to a new approach to developing drugs to treat cancer patients.
"Our research implies that by shutting off a critical cancer gene, tumour cells can realize that they are broken and restore this physiologic fail-safe program," said Felsher, the senior author of the study published online in the Proceedings of the National Academy of Sciences.
The gene that the researchers studied produces a protein called Myc (pronounced "mick"), which promotes cell division. A mutation of the gene causes cells to overproduce the protein, prompting perpetual cell division and tumour growth.
When the researchers turned off the mutated gene, they found that not only did uncontrolled cell division cease, but the cells also reactivated a normal physiological mechanism, called senescence, which makes it possible for a cell to eventually die.
"What was unexpected was just the fact that cancer cells had retained the ability to undergo senescence at all," said Felsher.
The researchers worked with a series of mice engineered to have Myc-triggered cancers of either the liver, blood or bones, along with a specially constructed version of the Myc gene that they could switch off by feeding the mice antibiotics. When the mice were administered the drugs, the tumours ceased growing and then diminished, with some disappearing over the course of just a few days.
This is the first time that cancer researchers have explored the idea that senescence might play a key role in diminishing tumours; most of the previously conducted studies focused on reactivating tumour-suppressor genes, which are generally overcome by a proliferating cancer.
Dr. Felsher described senescence as acting like a fail-safe mechanism to stop cancer. When a cell detects a deleterious mutation, it launches the senescence process, resulting in the permanent loss of the cell's ability to proliferate, thus halting any cancer.
"In order to become tumour cells, those cells have to overcome senescence," said Dr. Chi-Hwa Wu, postdoctoral researcher in Felsher's lab and first author of the study.
Dr. Felsher considers it a cell version of the Jekyll and Hyde transformation.
"It's sort of like Mr. Hyde realizing that there's something wrong with him and then being able to put himself back into his normal state as Dr. Jekyll," he said.
The researchers are now planning to test how well the approach works in human cancer cells.
"And we're also trying to figure out what the mechanism is. What are the molecular mechanisms of this, so that we can figure out how to better treat cancer," Felsher said.