In 10 seconds? Almost all cancers are affected by abnormal RNA splicing. Cancer researchers are leveraging this knowledge to design innovative cancer treatments.

What the heck is RNA splicing? What a great segue into one of my favorite topics: breaking down cell biology! OK. I like to compare our bodies to restaurants, and describe the DNA inside our cells as a recipe book that provides instructions on how to make everything in our body. In this analogy, RNA can be described as individual orders or recipes for particular dishes. These orders are then turned into the dishes–AKA proteins–which are the cellular units that perform the vast majority of cellular activities.

Very cute, but where are you going with this? Bear with me! RNA splicing is an essential cellular process where RNA ‘recipes’ are cut and pasted together in different ways to produce completely different protein end-products. It’s like if you cut out different ingredients from a cake recipe you could end up with a recipe for cookies, pie crust, or pasta.

Unconventional RNA splicing can lead to many downstream consequences in protein function or production levels. Source: Bradley RK and Anczuków O. Nat Rev Can. 2023; 23:125-155

Got it. So what does RNA splicing have to do with cancer? Right. When RNA splicing machinery (the proteins responsible for splicing RNA) goes awry, so does cellular activity–which can pave the way for cancer. Since RNA splicing precedes protein formation (Remember it goes DNA→RNA→protein) and impacts the formation of many different types of proteins, scientists hope that RNA splicing therapies could be more impactful than individual protein-targeted cancer treatments (like Ras inhibitors for example). To that point, scientists are unraveling the ways that RNA splicing machinery is commonly altered in cancer and working to make cancer treatments based on their findings.

What sorts of treatments? Scientists first started designing drugs that inhibit the function of some of the most important components in RNA splicing, noting that cancerous cells tended to be more susceptible to these drugs than healthy cells. However, when these drugs were tested in patients, some dangerous side effects were noted–likely because RNA splicing is essential for healthy cells as well. Because of this, many researchers have turned their attention to designing treatments to inhibit more peripheral players in RNA splicing. Many studies are underway, although no RNA-splicing cancer treatments have been FDA-approved yet.

Are there any other ways knowledge of RNA splicing might be useful to cancer patients? Yes! Some scientists think deeper knowledge of RNA splicing alterations in cancer could help design immunotherapies like cancer vaccines. This is because altered RNA ‘recipes’ due to altered RNA splicing can lead to the formation of wonky proteins. These proteins could form the basis of a vaccine that could direct the immune system to kill cancerous cells with these unique proteins (similar to how the immune system can recognize virus-specific proteins inside cells and spare healthy cells). However, it’s known that not all RNA ‘recipes’ get turned into proteins and not every cell in a tumor has the same unique proteins, so this approach to cancer treatment still needs further optimization. Even with all this progress, there’s still so much to learn about RNA splicing and cancer. It’ll be exciting to monitor how this field develops!

RNA ≠ Protein: Don’t Count Your Chickens Before They Hatch

Technology has advanced so that scientists can get a readout of all the RNA transcripts from a single cell or a group of cells (kind of how restaurants can have computer systems that track all the food orders). These tools (transcriptome analysis or RNAseq) allow scientists to gain a better understanding of cellular functioning.

While useful, there’s a key limitation to these studies. Just because there’s an RNA ‘recipe’, it doesn’t necessarily mean that it’ll be turned into a protein–just how some restaurant orders may not be fulfilled if they run out of a key ingredient, or if an order is canceled. That’s why scientific analysis based off RNA sequencing studies must be interpreted with caution.

Dr. Talia Henkle has distilled 8 papers saving you 31.5  hours of reading time.

This Science Integrity Check of this 3-min Science Digest was performed by Flávia Oliveira Geraldes