die seems to be different than what was previously thought. Scientists have discovered a new method of cancer cell death, which is caused by the Schlafen11 gene. This finding is surprising because even though chemotherapy has been used to treat cancer for many years, this particular way in which cancer cells die has never been seen before. Further research is needed to understand when and where this occurs in patients. The implications of this discovery could potentially impact the treatment of cancer patients in the future.Researchers from the Netherlands Cancer Institute, led by Thijn Brummelkamp, have discovered a new way in which cancer cells die. They found that the Schlafen11 gene plays a role in this process, which was unexpected. This finding is significant because it has never been observed before, despite almost a century of chemotherapy treatments for cancer patients. Further investigation is needed to understand where and when this occurs in patients. The researchers believe that this discovery could have important implications for the treatment of cancer patients. Their findings have been published in Science.
Cancer treatments can harm the DNA of cells, which can lead to the cells initiating their own death when the damage becomes too severe. The protein p53 is responsible for ensuring that damaged DNA is repaired, but it also triggers cell suicide when the damage is irreparable. This process helps to prevent uncontrolled cell division and the formation of cancer.
Surprise: an unanswered question
Despite this seemingly foolproof system, the reality is more complicated. According to Thijn Brummelkamp, “In over half of tumors, p53 is no longer functional and does not play a role.” This raises the question: why do cancer cells without p53 still die when their DNA is damaged?
Is it possible to alter cells’ DNA in order to make them resistant to chemotherapy or radiation? Much to my surprise, this question went unanswered.”
Following this, his research team, alongside Reuven Agami’s group, made a groundbreaking discovery about a previously unknown method of cell death after DNA damage. In their experiments, they treated cells with chemotherapy after carefully modifying their DNA. Thijn explained, “We were searching for a genetic alteration that would enable cells to survive chemotherapy. Our team has extensive experience in selectively disabling genes, which we were able to apply effectively in this case.”
Discovering a new key player in cell death
Through gene manipulation, the researchers were able to uncover a previously unrecognized mechanism of cell death after DNA damage.The research group has identified a new way that cells can die, and it is controlled by the gene Schlafen11 (SLFN11). According to principal investigator Nicolaas Boon, when DNA damage occurs, SLFN11 stops the production of proteins in cells, specifically the ribosomes. This causes a lot of stress in the cells, ultimately leading to their death. This newly discovered pathway to cell death does not rely on the p53 gene.
The SLFN11 gene is already known in cancer research. It is often inactive in tumors of patients who do not respond to chemotherapy. According to Thijn, this new discovery helps explain this connection. Without SLFN11, cells will not die in response to DNA damage, allowing the cancer to continue growing.
“This finding has a significant impact on cancer treatment,” says Thijn. “It raises many new research questions, which is typical of fundamental research. We have confirmed our discovery in cancer cells grown in the lab, but there are still crucial questions to be answered: Where and when does this pathway occur in patients? How does it impact immunotherapy or chemotherapy? Does it affect the side effects of cancer therapy? If this type of cell death also plays a substantial role in patients, it will have implications for cancer treatments. These are important questions that need to be explored.”
Researchers are working on understanding the functions of the thousands of genes that people have. To do this, Thijn Brummelkamp developed a method using haploid cells, which only have one copy of each gene. This is different from regular cells in our bodies, which have two copies of each gene. Having two copies can make it challenging to observe the effects of mutations, as changes often occur in just one of the copies. Brummelkamp and his colleagues are using this method to unravel various processes.
that has been fundamental in understanding various diseases for many years using this adaptable method. For instance, his team recently uncovered that cells have the ability to produce lipids in a manner that was previously unknown. They also revealed the mechanism by which certain viruses, including the deadly Ebola virus, are able to penetrate human cells. Additionally, they investigated how cancer cells develop resistance to specific treatments and identified proteins that inhibit the immune system, a finding that has implications for cancer immunotherapy. In the past few years, his research team has identified two enzymes that had been elusive for over four decades, and that turned out to be essential for muscle function and brain development.
The research was funded by KWF Dutch Cancer Society, Oncode Institute, and Health Holland. Â
