Researchers at Yale University recently made a breakthrough in understanding why cancer cells often have an extra chromosome, and how it contributes to tumour growth. This understanding may help design new therapies that target this genetic material, specifically to turn it off, to potentially improve the treatment of the disease.
The study, published in the journal Science, revealed that additional chromosomes (aneuploidy) could play a crucial role in the growth of tumours, solving a decades-old mystery. The researchers showed this by using gene-editing technology CRISPR to remove entire chromosomes from cancer cells in the lab.
Researchers were not sure whether the extra chromosomes were causing cancer in the first place or if the mutation happens because of cancer.
Chromosomes are thread-like structures that are present inside the nucleus of cells. Each chromosome is made of a protein and a single DNA molecule.
The cancer chromosomes
Using CRISPR the researchers focused on removing chromosome 1, which was thought to be associated with the progression of cancer and appears early in the development of the disease, from cancerous tumour cells in the lab.
“Being able to manipulate aneuploid chromosomes in this way will lead to a greater understanding of how they function,” Jason Sheltzer, assistant professor of surgery at Yale School of Medicine and senior author of the study explained, referring to the newly developed approach they named Restoring Disomy in Aneuploid cells using CRISPR Targeting (ReDACT).
“When we eliminated aneuploidy [the extra chromosome] from the genomes of these cancer cells, it compromised the malignant potential of those cells and they lost their ability to form tumours,” Sheltzer pointed out, indicating the significance of their findings in selectively targeting aneuploid cells.
The finding suggests that cancer cells may depend on extra chromosomes to grow and survive. The researchers also discovered that multiple genes on this additional chromosome contributed to the growth of cancer cells when they are overrepresented.
To understand this concept better, let us use an analogy. Imagine a bustling city where buildings represent cells in the body. In this city, normal cells are like regular, well-constructed buildings, while cancer cells are like buildings with extra floors. The extra floors symbolise the presence of extra chromosomes in cancer cells.
Within these extra floors, specific rooms (genes) play a significant role in promoting the growth of cancer cells when they are overrepresented. It is like certain rooms contain elements that fuel the growth and proliferation of cancer cells.
The researchers found that by targeting these specific rooms on the extra floors, it is as if they have found a way to selectively turn off the elements within those rooms. By doing so, they weaken the cancer cells and hinder their ability to grow and spread.
It is suspected that cancer cells may exhibit an ‘aneuploidy addiction’ due to the prevalence of aneuploidy in almost all cancers. Targeting these aneuploid cells selectively could offer a promising approach to combat cancer, potentially minimising the effect on normal, non-cancerous tissue.
Future of cancer treatments
If this concept holds up, cancer could be treated by targeting these specific genes within the extra chromosome to slow or stall the growth of malignant cells. This would also spare healthy cells in the body that do not contain the extra genetic material, solving one of the biggest problems in today’s cancer therapies.
The next steps for the research team will involve conducting studies on animals to further explore these findings. They will also investigate which drugs could be best suited to target the extra chromosomes and potentially collaborate with pharmaceutical companies to test these approaches in clinical trials.
This finding could have the potential to revolutionise cancer treatment. By understanding the role of extra chromosomes in cancer cells, we can develop new strategies to specifically target and treat cancer while minimising harm to healthy cells.
“We’re very interested in clinical translation. So, we’re thinking about how to expand our discoveries in a therapeutic direction,” says Sheltzer emphasising their goal of advancing their research towards clinical trials and potential cancer treatments.
