More than 16,000 Australians will be diagnosed with melanoma each year. Most of these will be caught early, and can be cured by surgery.

However, for patients with advanced or metastatic melanoma, which has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (that attack specific cancer traits) and immune therapies (that leverage the immune system). Over the past decade, these treatments have seen a significant climb in the number of advanced melanoma patients surviving for at least five years after diagnosis, from less than 10% in 2011 to around 50% in 2021.

While this is great news, there are still many melanoma patients who cannot be treated effectively with current therapies. Researchers have developed two exciting new therapies that are being evaluated in clinical trials for advanced melanoma patients. Both involve the use of immunotherapy at different times and in different ways.

The first results from these trials are now being shared publicly, offering insight into the future of melanoma treatment.

Immunotherapy before surgery

Immunotherapy works by boosting the power of a patient’s immune system to help kill cancer cells. One type of immunotherapy uses something called “immune checkpoint inhibitors”.

Immune cells carry “immune checkpoint” proteins, which control their activity. Cancer cells can interact with these checkpoints to turn off immune cells and hide from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system activated to fight the cancer.

Results from an ongoing phase 3 trial using immune checkpoint inhibitors were recently published in the New England Journal of Medicine.

This trial used two types of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.

Some 423 patients (including many from Australia) were enrolled in the trial, and participants were randomly assigned to one of two groups.

The first group had surgery to remove their melanoma, and were then given immunotherapy (nivolumab) to help kill any remaining cancer cells. Giving a systemic (whole body) therapy such as immunotherapy after surgery is a standard way of treating melanoma. The second group received immunotherapy first (nivolumab plus ipilimumab) and then underwent surgery. This is a new approach to treating these cancers.

Based on previous observations, the researchers had predicted that giving patients immunotherapy while the whole tumour was still present would activate the tumour-fighting abilities of the patient’s immune system much better than giving it once the tumour had been removed.

Sure enough, 12 months after starting therapy, 83.7% of patients who received immunotherapy before surgery remained cancer-free, compared to 57.2% in the control group who received immunotherapy after surgery.

Based on these results, Australian of the year Georgina Long – who co-led the trial with Christian Blank from The Netherlands Cancer Institute – has suggested this method of immunotherapy before surgery should be considered a new standard of treatment for higher risk stage 3 melanoma. She also said a similar strategy should be evaluated for other cancers.

The promising results of this phase 3 trial suggest we might see this combination treatment being used in Australian hospitals within the next few years.

mRNA vaccines

Another emerging form of melanoma therapy is the post-surgery combination of a different checkpoint inhibitor (pembrolizumab, which blocks PD-1), with a messenger RNA vaccine (mRNA-4157).

While checkpoint inhibitors like pembrolizumab have been around for more than a decade, mRNA vaccines like mRNA-4157 are a newer phenomenon. You might be familiar with mRNA vaccines though, as the biotechnology companies Pfizer-BioNTech and Moderna released COVID vaccines based on mRNA technology.

mRNA-4157 works basically the same way – the mRNA is injected into the patient and produces antigens, which are small proteins that train the body’s immune system to attack a disease (in this case, cancer, and for COVID, the virus).

However, mRNA-4157 is unique – literally. It’s a type of personalised medicine, where the mRNA is created specifically to match a patient’s cancer. First, the patient’s tumour is genetically sequenced to figure out what antigens will best help the immune system to recognise their cancer. Then a patient-specific version of mRNA-4157 is created that produces those antigens.

The latest results of a three-year, phase 2 clinical trial which combined pembrolizumab and mRNA-4157 were announced this past week. Overall, 2.5 years after starting the trial, 74.8% of patients treated with immunotherapy combined with mRNA-4157 post-surgery remained cancer-free, compared to 55.6% of those treated with immunotherapy alone. These were patients who were suffering from high-risk, late-stage forms of melanoma, who generally have poor outcomes.

It’s worth noting these results have not yet been published in peer-reviewed journals. They’re available as company announcements, and were also presented at some cancer conferences in the United States.

Based on the results of this trial, the combination of pembrolizumab and the vaccine progressed to a phase 3 trial in 2023, with the first patients being enrolled in Australia. But the final results of this trial are not expected until 2029.

It is hoped this mRNA-based anti-cancer vaccine will blaze a trail for vaccines targeting other types of cancer, not just melanoma, particularly in combination with checkpoint inhibitors to help stimulate the immune system.

Despite these ongoing advances in melanoma treatment, the best way to fight cancer is still prevention which, in the case of melanoma, means protecting yourself from UV exposure wherever possible.

Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) and John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Pratik Raul, University of Canberra; Jeroen van Boxtel, University of Canberra, and Jovana Acevska, University of Canberra

Autism is a neurodevelopmental difference associated with specific experiences and characteristics.

For decades, autism research has focused on behavioural, cognitive, social and communication difficulties. These studies highlighted how autistic people face issues with everyday tasks that allistic (meaning non-autistic) people do not. Some difficulties may include recognising emotions or social cues.

But some research, including our own study, has explored specific advantages in autism. Studies have shown that in some cognitive tasks, autistic people perform better than allistic people. Autistic people may have greater success in identifying a simple shape embedded within a more complex design, arranging blocks of different shapes and colours, or spotting an object within a cluttered visual environment (similar to Where’s Wally?). Such enhanced performance has been recorded in babies as young as nine months who show emerging signs of autism.

How and why do autistic individuals do so well on these tasks? The answer may be surprising: more “neural noise”.

What is neural noise?

Generally, when you think of noise, you probably think of auditory noise, the ups and downs in the amplitude of sound frequencies we hear.

A similar thing happens in the brain with random fluctuations in neural activity. This is called neural noise.

This noise is always present, and comes on top of any brain activity caused by things we see, hear, smell and touch. This means that in the brain, an identical stimulus that is presented multiple times won’t cause exactly the same activity. Sometimes the brain is more active, sometimes less. In fact, even the response to a single stimulus or event will fluctuate continuously.

Neural noise in autism

There are many sources of neural noise in the brain. These include how the neurons become excited and calm again, changes in attention and arousal levels, and biochemical processes at the cellular level, among others. An allistic brain has mechanisms to manage and use this noise. For instance, cells in the hippocampus (the brain’s memory system) can make use of neural noise to enhance memory encoding and recall.

Evidence for high neural noise in autism can be seen in electroencephalography (EEG) recordings, where increased levels of neural fluctuations were observed in autistic children. This means their neural activity is less predictable, showing a wider range of activity (higher ups and downs) in response to the same stimulus.

In simple terms, if we imagine the EEG responses like a sound wave, we would expect to see small ups and downs (amplitude) in allistic brains each time they encounter a stimulus. But autistic brains seem to show bigger ups and downs, demonstrating greater amplitude of neural noise.

Many studies have linked this noisy autistic brain with cognitive, social and behavioural difficulties.

But could noise be a bonus?

The diagnosis of autism has a long clinical history. A shift from the medical to a more social model has also seen advocacy for it to be reframed as a difference, rather than a disorder or deficit. This change has also entered autism research. Neuroaffirming research can examine the uniqueness and strengths of neurodivergence.

Psychology and perception researcher David Simmons and colleagues at the University of Glasgow were the first to suggest that while high neural noise is generally a disadvantage in autism, it can sometimes provide benefits due to a phenomenon called stochastic resonance. This is where optimal amounts of noise can enhance performance. In line with this theory, high neural noise in the autistic brain might enhance performance for some cognitive tasks.

Our 2023 research explores this idea. We recruited participants from the general population and investigated their performance on letter-detection tasks. At the same time, we measured their level of autistic traits.

We performed two letter-detection experiments (one in a lab and one online) where participants had to identify a letter when displayed among background visual static of various intensities.

By using the static, we added additional visual noise to the neural noise already present in our participants’ brains. We hypothesised the visual noise would push participants with low internal brain noise (or low autistic traits) to perform better (as suggested by previous research on stochastic resonance). The more interesting prediction was that noise would not help individuals who already had a lot of brain noise (that is, those with high autistic traits), because their own neural noise already ensured optimal performance.

Indeed, one of our experiments showed people with high neural noise (high autistic traits) did not benefit from additional noise. Moreover, they showed superior performance (greater accuracy) relative to people with low neural noise when the added visual static was low. This suggests their own neural noise already caused a natural stochastic resonance effect, resulting in better performance.

It is important to note we did not include clinically diagnosed autistic participants, but overall, we showed the theory of enhanced performance due to stochastic resonance in autism has merits.

Why this is important?

Autistic people face ignorance, prejudice and discrimination that can harm wellbeing. Poor mental and physical health, reduced social connections and increased “camouflaging” of autistic traits are some of the negative impacts that autistic people face.

So, research underlining and investigating the strengths inherent in autism can help reduce stigma, allow autistic people to be themselves and acknowledge autistic people do not require “fixing”.

The autistic brain is different. It comes with limitations, but it also has its strengths.

Pratik Raul, PhD candidiate, University of Canberra; Jeroen van Boxtel, Associate professor, University of Canberra, and Jovana Acevska, Honours Graduate Student, University of Canberra

This article is republished from The Conversation under a Creative Commons license. Read the original article.