Ovarian cancer kills more women than any other cancer of the female reproductive system, ranking fifth in women’s cancer deaths. For the first time, researchers at Tel Aviv University used the protein CKAP5 (cytoskeleton-associated protein) as a therapeutic target for RNA-based nanodrugs in a study. The researchers targeted cells in the tissues of ovarian cancer with lipid nanoparticles containing RNA for silencing CKAP5, causing the cells to collapse and achieving an 80 percent survival rate in animal models after identifying a genetically unstable mutation that was resistant to both chemotherapy and immunotherapy.
“Through the precise delivery of an RNA drug, we were able to silence [the CKAP5] protein for the first time using the lipid nanoparticles developed by Prof. Peer.” According to Dr. Sushmita Chatterjee, “We proved that CKAP5, a protein responsible for the stability of the cell, can be silenced and that this procedure collapses and destroys the entire cancer cell.”
Designated conveyance of an RNA drug
The advancement was accomplished by a TAU research group driven by Prof. Dan Companion of The Shmunis Institute of Biomedicine and Malignant Growth Exploration, a worldwide trailblazer in the improvement of RNA-based drugs, Top of the Research Facility of Accuracy Nanomedicine, and TAU’s VP for Research and Development; furthermore, by Dr. Sushmita Chatterjee, a post-doctoral understudy from India at Prof. Friend’s lab, as a team with Prof. David Sprinzak of The George S. Insightful Staff of Life Sciences and Prof. Ronen Zaidel-Bar of the Sackler Personnel of Medication. The findings were presented and discussed in Science Advances.
“Because there is currently no known method to silence the protein CKAP5, it has never been studied in relation to the fight against cancer.”
Dr. Sushmita Chatterjee, post-doctoral student from India at Prof. Peer’s lab
According to Dr. Chatterjee, “the protein CKAP5 has never been studied in relation to the fight against cancer, simply because there is no known way to silence it.” Through the precise delivery of an RNA drug, we were able to silence this protein for the first time using Prof. Peer’s lipid nanoparticles. We demonstrated that the cancer cell’s stability-regulating protein, CKAP5, can be silenced and that this destroys the entire cell.”
The new CKAP5-silencing RNA drug was tested on 20 types of cancer in the second phase of the study. This procedure proved more effective against some cancer cells than against others. It was discovered that the silencing of CKAP5 made cancers with high genetic instability, which are typically extremely resistant to chemotherapy, particularly vulnerable.
“As researchers, we play a game that is similar to dominoes: we always look for the one component of the cancer’s structure that is so crucial that removing it would result in the cell’s collapse as a whole. Prof. Dan Peer asserts, “CKAP5 is such a domino piece, and we are already working on additional applications.”
Dr. Chatterjee asserts, “All cancer cells are genetically unstable.” Any other way, they would be solid, not destructive. There are, however, various degrees of genetic instability. We discovered that damage to CKAP5 affects cancer cells that are more unstable way, they would be solid, not destructive. There are, however, various degrees of genetic instability. We discovered that damage to CKAP5 affects cancer cells that are more unstable. They were pushed to their limits by our medication, which effectively destroyed their structure. By suppressing the defective protein with RNA, our plan was to transform the characteristic of genetic instability into a threat to these cells. We showed interestingly that CKAP5 can be utilized to kill malignant growth cells, and afterward we noticed the natural component that makes the disease cells breakdown in the protein’s nonappearance.”
Furnished with these bits of knowledge, the scientists tried the new medication in a creature model for ovarian malignant growth, accomplishing an endurance pace of 80%.
Prof. Peer says, “We chose ovarian cancer because it’s a good target.” This type of cancer is extremely sensitive to the silencing of CKAP5, despite being extremely resistant to both chemotherapy and immunotherapy. The fact that the CKAP5 protein is a brand-new target in the fight against cancer should be emphasized. Focusing on cell division isn’t new; however, utilizing RNA to target proteins that make up the cell’s skeleton (cytoskeleton) is another methodology and another objective that should be additionally explored. In our capacity as researchers, we are playing a dominoes game: we always look for the one component of the cancer’s structure that is so crucial that removing it would result in the cell’s collapse as a whole. We are already working on additional applications, this time in blood cancers, because CKAP5 is such a pivotal piece.
More information: Sushmita Chatterjee et al, Therapeutic gene silencing of CKAP5 leads to lethality in genetically unstable cancer cells, Science Advances (2023). DOI: 10.1126/sciadv.ade4800
