Scientists first noticed this phenomenon when examining cancer cells under a microscope. Early 1900’s. As cancer cells proliferate, they Some ended up with too many gene-carrying chromosomes, the structures we know today. Some say there was too little left over.
This shocking observation has led German embryologists to propose that abnormal chromosome numbers aren’t just a hallmark of cancer, perhaps they cause it. This idea fell out of favor as scientists discovered dozens of individual genes that cause cancer and began developing drugs to target them.
However, chromosomal aberrations in cancer cells remained a strange invisible phenomenon common to 90% of cancers. Everyone knew it was there. No one knew why or what it meant.
“It was certainly overlooked to some extent, but the reason was that it was very difficult to study,” said Uli Bendavid, an associate professor of human molecular genetics and biochemistry at Tel Aviv University who was not involved in the new project. That’s why,” he said. study. “For decades it was ignored. It was like an elephant in a cancer lab.”
In a new study, scientists have discovered a way to tackle the mystery using a clever CRISPR hack. Their work showed that without an extra chromosome, certain cancer cells cannot seed tumors in animals.
Cancer Drivers or Downstream Impacts?
Humans have 23 pairs of chromosomes, long thread-like structures made up of DNA and proteins that carry genes. Normally, when a cell divides, chromosomes make copies of themselves and segregate into new cells in an orderly and symmetrical fashion. In cancer, however, this phenomenon is complicated and the cells end up with an abnormal number of chromosomes.
For decades, classic conundrums in science have hampered the study of this phenomenon. Are the abnormalities the cause of cancer, or are they just signs that something is already wrong within the cell? At the time, adding or removing chromosomes was not easy, so science was looking for answers. researchers had to rely primarily on interesting correlations.
In one study, melanoma cells were exposed to chemicals to further destroy their chromosomes.those cells Easier to develop tolerance This suggests that chromosomal aberrations may play a role in cancer’s ability to block drugs.another study found that the more chromosomally unstable a patient’s tumor cells were, the more likely the cancer was to be aggressive and have a poor prognosis.
Again, the question of cause and effect loomed. Is it possible that chromosomal disruptions play a role in these cancers, or is it just a downstream effect?
The invention of CRISPR gene-editing technology ten years ago allowed scientists to add, delete, or fine-tune genes. But deleting entire chromosomes is another matter.
To do serious chromosome engineering, cancer biologist Jason Scherzer and his team at the Yale School of Medicine had to deploy a CRISPR hack. First, they inserted the herpes virus gene into an extra chromosome of cancer cells. First, they chose chromosome 1q. This is one of the first chromosomes to gain or lose extra copies during breast cancer development.
They then used the herpes drug ganciclovir to target the altered chromosome. The technique killed cells with extra copies, leaving cancer cells with the normal number of chromosomes.
When they tried to grow tumors from this subpopulation of cancer cells, they found that the cells were no longer able to seed Petri dishes or live mice. For Scherzer, this was clear evidence that the extra chromosome was not just an effect, but a driver of the disease.
“It plays a central role,” Scherzer said.
A new way to attack cancer
For now, this technique is a tool, not a cure. It is not yet feasible to consider restoring the normal number of chromosomes in cancer cells as a way to prevent disease.
But it could point to other ways to target cancer in the future. Our understanding of cancer genetics has led to the development of therapies that target specific mutations that drive cancer progression. However, cancer is an insidious enemy and is often resistant to any treatment.
The recognition that extra chromosomes are important in cancer progression means that researchers can attack cells with extra chromosomes in new ways to find and kill them.
Since chromosomes contain hundreds or thousands of genes, such an approach could expand the number of targets. Even if cancers eventually become “resistant” to such drugs by losing an extra chromosome, research suggests that doing so may also suppress their ability to cause cancer. are doing.
In essence, the extra chromosome becomes a new therapeutic vulnerability, Scherzer said. Because cells contain all other genetic material, such cells may “become sensitive to drugs that target genes, even if they are unrelated to cancer.” be.
