New drugs for ovarian cancer. Using RNA-based nanomedicine, researchers are achieving 80% survival rates in laboratory models
Ovarian cancer is the fifth leading cause of cancer death in women, causing more deaths than any other cancer of the female reproductive system. In a study conducted at Tel Aviv University, researchers used cytoskeleton binding protein (CKAP5) for the first time as a therapeutic agent for RNA-based nanomedicine. After finding mutations in genes that are resistant to both chemotherapy and immunotherapy in ovarian cancer tissue, the researchers targeted these cells with RNA to silence CKAP5 – causing the cell to die by up to 80% life in animal form.
Targeted delivery of RNA-based drugs
This progress was made by the TAU research team of Prof. Dan Peer of the Shmunis School of Biomedicine and Cancer Research, a global pioneer in RNA-based drug development, Head of the Precision Nanomedicine Laboratory and TAU Vice President for R&D; and by Dr. Sushmita Chatterjee, Indian post-doctoral student in the laboratory of Prof. Peer, in collaboration with Prof. David Sprinzak nke George S. Wise School of Life Sciences na Prof. Ronen Zaidel-Barr of the Sackler Medical School. The study was supported by the Rivkin Foundation for Ovarian Cancer Research and the Shmunis Family Foundation. The results were published in the scientific journal Science Advances.
“The CKAP5 protein has never been studied in relation to the fight against cancer, simply because there is no known way to shut it down,” Dr. Chatterjee explains. “The lipid nanoparticles developed by Professor Peer gave us the first opportunity to target this protein through the targeted delivery of drugs from RNA. We have shown that CKAP5, a protein responsible for cell stability, can be silenced, and this process fails and destroys all cancer cells.”
“Like a game of dominoes”
In the second phase of the study, the researchers tested the new drug RNA silencing CKAP5 on 20 types of cancer. Some cancer cells have been shown to be more sensitive than others to this process. Cancers with advanced genetic disorders, which are generally resistant to chemotherapy, are particularly sensitive to CKAP5 silencing.
“All cancer cells are genetically unstable,” said Dr. Chatterjee says. “Otherwise, they will be healthy, not cancer. However, there are different levels of genetics. We found that cancer cells, which are unstable, are also affected by the degradation of CKAP5. Our drugs pushed them to their limits and destroyed their structures. Our idea is to turn genetic instability into a threat to these cells, using RNA to silence the incorrect protein. We showed for the first time that CKAP5 can be used to kill cancer cells, and discovered a biological mechanism that causes cancer cells to die in the absence of the protein.”
Armed with this knowledge, researchers tested the new drug in animal models of ovarian cancer, achieving an 80% survival rate.
“We chose ovarian cancer because it’s a good target,” explains Professor Peer. Although resistant to both chemotherapy and immunotherapy, this type of cancer is highly sensitive to CKAP5 silencing. It should be emphasized that the CKAP5 protein is a new target in the fight against cancer. Protecting cell division is not new, but using RNA to target the proteins that make up the cell skeleton (cytoskeleton) – it is a new approach and a new goal that requires further research. As researchers, we are involved in something like a game of dominoes: we are always looking for a piece in the structure of cancer that is so important that if we remove it, the whole cell will fail . CKAP5 is this kind of domino, and we are working on other applications, this time in blood cancer.”
Source: Tel Aviv University
