RNA-based nanodrug treats ovarian cancer in mice

An 80 percent ovarian cancer survival rate in mice has been achieved using an RNA-based drug to silence the expression of a protein crucial to cancer cell division.

Ovarian cancer is the eighth most common cancer worldwide and accounts for 4.7 percent of cancer deaths among women. Initial treatment of ovarian cancer involves surgery and chemotherapy; however, 80-85 percent of patients develop chemo-resistance. This means that developing new treatments that are unaffected by this resistance is crucial. Professor Dan Peer and his team at Tel Aviv University, Israel, have developed an RNA-based nanodrug to silence the expression of a protein responsible for cell division called CKAP5, and published the results of their study in Science Advances.

'We proved that CKAP5, a protein responsible for the cell's stability, can be silenced, and that this procedure collapses and destroys the entire cancer cell', said Dr Sushmita Chatterjee, post-doctoral researcher, and lead author on the study.

Messenger RNA, or mRNA, is needed to produce proteins from the genetic information contained in DNA. Small interfering RNA (siRNA) is capable of disrupting gene expression without altering the DNA itself as it binds to mRNA, stopping gene expression. In this study, researchers delivered siRNA into the tumour encased in lipid nanoparticles to silence this specific protein target and cause cancer cell death.

Researchers showed cancer cell death was due to the cells' inability to initiate certain stages of cell division, due to the loss of this crucial protein. They said their findings mean that the protein CKAP5 is a good potential target for further research into ovarian cancer treatments.

The team hopes to validate the high survival rates seen by using a patient-derived mouse model, and further investigate how this therapy interacts with other treatments, as targeted therapies often result in cancer resistance. Dr Chatterjee said they are also interested in understanding the impact of this treatment on late-stage ovarian cancers, 'since the majority of ovarian cancer patients are diagnosed at late stages, it will be also interesting to investigate the therapeutic effects of CKAP5 silencing in a metastasised/late-stage cancer model'.