Revolutionising cancer treatment: the RNA breakthrough which could change everything

When Associate Professor Tamás Fischer speaks about his medical research project and its potential to change lives, he begins on a personal note.

“Unfortunately, I lost my mum to breast cancer, and it’s still kind of emotional,” he says, his voice catching.

“It was hard seeing her go through all the treatments and chemotherapies.”

It’s a painful reality that too many of us can relate to.

“There has been so much money and research put into cancer therapies, but most treatments still use toxic substances that only work because cancer cells are particularly sensitive to them,” says Fischer, a scientist from the John Curtin School of Medical Research at ANU.

“That’s not to say treatments aren’t improving, but the rest of the body suffers because it’s extremely hard to reliably distinguish between cancer cells and healthy cells.”

His experience inspired an innovative research idea. If successful, it could spare others from the same suffering.

“When my mum went through her treatment, I kept thinking, ‘There must be a way to find a treatment that only targets cancer cells’.”

Years later, researchers at The Shine-Dalgarno Centre for RNA Innovation are collaborating to develop therapies that target cancer cells with exceptional accuracy.

They are designing tiny ‘molecular robots’ made from RNA that can seek out and destroy cancer cells, while leaving healthy ones unharmed.

It’s a massive undertaking with extraordinary potential. Alongside Fischer, lab groups run by Associate Professor Marian Burr and Professor Thomas Preiss are adding their expertise to the cause.

“If this project works, it has the potential to change how we treat all cancers,” says Fischer.

“And it does work. We just need to make it work better.”

To see why RNA therapies could change cancer treatments in the future, we need to understand not just the biology of cancer, but also, how life itself began.

Avoiding cancer’s defences

One of the reasons why cancer is so difficult to treat is because it disguises itself as part of our own body.

“In a way, they are just our cells,” explains Fischer.

As a result, treatments like chemotherapy and radiotherapy end up harming healthy tissue too.

“Cancer treatment is already so much better than 20 to 30 years ago,” he says.

“But people still have to go through some challenging therapies with bad side effects.”

In addition to common side effects of radiation therapy and chemotherapy such as nausea and tiredness, these therapies can also cause long term damage to the heart, lungs and other organs. And debilitating fatigue is another big issue for patients undergoing chemotherapy, which can remain for a significantly long time after treatment.

Fischer says that for many cancer survivors, the “quality of life is probably never going to be like before the cancer diagnosis”.

Even our best treatments have unwanted side effects

Burr is leading the clinical side of the project, linking the advances in research with patient outcomes.

As a Snow Fellow she is also investigating ways to harness the power of the immune system to target and eradicate cancer more effectively than chemotherapy and radiotherapy.

“My lab works on lung cancer treatments,” she says.

“Unfortunately, most patients with lung cancer present with advanced disease that has already metastasised and spread to other parts of the body.

“Many therapies can be used, but they are often not curative.”

New immunotherapies are paving the way for better treatments by blocking molecular ‘off switches’ that cancer cells use to hide from the immune system. But there is still room for improvement.

“The survival rate of metastatic melanoma used to be less than five percent,” Burr says. “With immune checkpoint inhibitor therapies, over half of patients are surviving long term.”

But these therapies can also cause the immune system to attack healthy tissues too.

“They can cause systemic inflammation in almost every organ.”

Another big challenge is that cancer cells adapt over time, making even the best treatments less effective.

“This led us to try to develop an approach that specifically targets the cancer cells themselves, avoiding effects on normal, healthy tissues.”

Engineering a smart weapon to fight cancer from within

Unlike traditional treatments that attack from the outside, this new approach aims to fight cancer from the inside out.

“We are making little molecular robots that can enter any cell and screen for a feature unique to a person’s specific cancer,” says Fischer.

The technology harnesses the very nature of life itself and is an elegant example of the untapped potential of biochemical engineering.

“The central dogma has been that DNA is copied into RNA, and RNA is used to make a protein,” says Fischer.

“But it’s now very clear that RNA does much more than this. It’s not just a messenger. It has another life inside the cell. And it can do similar things to a protein, including catalysing reactions.”

This discovery has led scientists to hypothesise that early life on Earth was first based on RNA molecules, not DNA, with RNA acting as both genetic material and as catalysts for biochemical reactions.

By taking advantage of this Swiss-army-knife-like functionality, the researchers hope to engineer RNA to search and destroy cancer cells.

First, the RNA-based ‘molecular robot’ will check if it’s inside a cancer cell. If it is, it then activates itself and triggers a reaction that helps kill the cancer cell from the inside and other cancer cells nearby.

A more personalised approach

By leveraging recent advances in medicine, the researchers plan to program their RNA treatment to seek out mutations specific to an individual’s cancer.

“For every person, their cancer cells are unique,” says Fischer.

Using genome sequencing, doctors can now pinpoint genetic code unique to that person’s cancer cells.

“Once we have this sequence then we can program our RNA to only activate when they find this specific feature.”

The RNA remains inactive in the rest of the body and will disappear within a few weeks after administration.

An advantage to RNA-guided therapies as opposed to other possible approaches such as more permanent gene-editing technologies, is reduced risks.

“With genome editing, once it’s edited, the genome always stays like that,” says Fischer.

“But with RNA, you can do very similar things except it doesn’t get into our genome. It’s only a temporary change.”

There is still much important work ahead before the researchers move forward with the technology.

“Our approach is working in human cell cultures, but it’s not very efficient yet.”

One way that they are looking to optimise this process is by mining an untapped resource of the thousands of different RNA mechanisms used in bacteria and fungi to catalyse biological reactions.

Convincing cancer cells to initiate their own defeat

While Fischer and his lab fine-tunes the molecular robot’s efficiency, Burr is working on programming a destroy function that will only target the cancer cells.

“The beauty of this system is that you could engineer it to express anything that you like,” she says.

“If you could make cancer cells express certain proteins, the immune system could come in and destroy the cancers.”

She is investigating ways to make the ‘cold’ tumour ‘hot’ and visible to the immune system.

Using this model, RNA therapy could both directly kill the cancer cell and get the cell to secrete immune-activating molecules into the microenvironment of the tumour.

“As well as directly targeting cancer cells, it could also take out neighbouring cells.”

By harnessing the versatile nature of RNA, they hope to offer a solution that is both highly specific and adaptable to individual patients.

“Theoretically, any cancer could be treated with this method,” says Fischer.

RNA has the potential to treat many diseases

The work is not just an exciting frontier in cancer treatment, but a continuation of a long history of RNA research at the University.

This legacy stretches back to the early 1970s when two ANU scientists, Lynn Dalgarno and his PhD student John Shine, made a breakthrough in understanding how bacteria read genetic instructions.

This significant discovery, now known as the Shine-Dalgarno sequence, laid the foundation for major advancements in molecular biology and genetic engineering.

Fifty years on, Preiss is leading the Shine-Dalgarno Centre for RNA Innovation to harness the potential of RNA for medicine.

“RNA therapy is just exploding,” says Preiss.

“We already know how to package mRNAs and how to synthesise them.”

Preiss says that RNA technology is set to revolutionise medicine, not just in treating cancer but in addressing a wide range of diseases.

“In the future, RNA technology will be a platform, not just for vaccines but for many other things as well,” he explains.

This adaptability is what makes RNA-based therapies so powerful. Instead of designing entirely new treatments from scratch, scientists can modify existing RNA structures to target different diseases.

“You don’t have to redesign the whole system. We can very easily adjust, accelerating the speed of applying it to various diseases.”

With RNA-based therapies inspiring researchers worldwide, it’s clear that a significant leap in cancer therapy is coming.

“In the future, cancer treatments will probably be entirely RNA-based,” predicts Fischer.

But there is still a long road ahead.

The next steps for the researchers at ANU will be demonstrating their platform’s efficacy before progressing to mouse models and finally clinical trials. As with all technological advances, there are also risks of failure along the way.

“We all believe that this will actually work,” Fischer says.

“I don’t know if we will be the first to make it work or if someone else will, but it will work.”

He is optimistic due to the potential of the team at the Shine-Dalgarno Centre for RNA Innovation.

“I have hope because I fully believe in my people,” he says. “Alongside Marian and Thomas, we also have students and postdocs who are just so amazing. They are so switched on because they want to see where this can go.”

This optimism extends to the broader implications of RNA technology.

“If you asked me 10 years ago whether we will ever have a cure for cancer, I would have said no because everyone’s cancers are so different.

“Now I think we could actually have the research needed to solve cancer in 10 to 15 years, with future treatment having almost no side effects.”

It’s a big call, but for Fischer, we have no choice but to aim high.

“For my mum, it’s too late,” he says. “But I really hope that people won’t have to go through such awful treatments in the future.”

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This article first appeared at the College of Science and Medicine.