Scientists discovered a new activator called L687 that can prompt cancer cells to accept antisense oligonucleotide (ASO) drugs. These drugs work by blocking messages from genes that promote cancer growth. Previous methods for delivering ASOs into cells were not very successful. The findings from this research will help speed up the development and delivery of new ASO cancer treatments.
Antisense oligonucleotides (ASOs) are a type of advanced medication that can block harmful messages from our genes, helping to treat diseases. For individuals with cancer, ASOs have the potential to block messages that fuel the growth of cancer.
ASOs are not currently used to treat cancer because they need to be delivered inside cancer cells, but the cells have gatekeeper molecules that prevent unwanted substances from entering. This has made it challenging to find an effective ASO delivery system, despite various attempts to bypass the gatekeepers.
A recent study published in the journal Nucleic Acids Research by researchers from Osaka University has identified a method for delivering ASOs to their target that could potentially overcome this obstacle.The team has successfully developed a new compound, L687, that targets specific calcium permeable channels on the surface of cancer cells. This compound opens the channels, allowing calcium to flow into the cells and signaling them to let in the ASOs. Lead author Hiroto Kohashi explains that the team discovered they could activate the TRPC3/C6 calcium permeable channels using L687. They also found that combining L687 with ASO resulted in efficient uptake of ASO into cancer cells during laboratory tests and in tumor cells inside mice. This led to the suppression of target gene activity.
ASO effectiveness has been improved.”
So far, ASOs have mostly been utilized for treating illnesses that cannot be cured and needed to be administered into the liver or spinal fluid. Based on the research by the Osaka team, L687 serves as a potent drug delivery system that could broaden the scope of ASO treatment to other areas of the body.
“We anticipate that our research findings will lead to significant advancements in the development and administration of ASOs and similar gene-targeting medications for cancer treatment,” stated senior author Masahito Shimojo.
The team is of the opinion that L687 could be an especially effective method for administering ASO therapy to lung or prostate cancer.cancers. These types of cancer cells contain numerous TRPC3/C6 calcium permeable channels1) that may be affected by L687, offering potential new targets for the latest generation of treatments.
1) TRPC3/C6 channels are part of the Transient Receptor Potential Canonical (TRPC) Channel subfamily within the TRP channel superfamily.
