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.

Have you ever heard something that others cannot – such as your name being called? Hearing voices or other noises that aren’t there is very common. About 10% of people report experiencing auditory hallucinations at some point in their life.

The experience of hearing voices can be very different from person to person, and can change over time. They might be the voice of someone familiar or unknown. There might be many voices, or just one or two. They can be loud or quiet like a whisper.

For some people these experiences are positive. They might represent a spiritual or supernatural experience they welcome or a comforting presence. But for others these experiences are distressing. Voices can be intrusive, negative, critical or threatening. Difficult voices can make a person feel worried, frightened, embarrassed or frustrated. They can also make it hard to concentrate, be around other people and get in the way of day-to-day activities.

Although not everyone who hears voices has a mental health problem, these experiences are much more common in people who do. They have been considered a hallmark symptom of schizophrenia, which affects about 24 million people worldwide.

However, such experiences are also common in other mental health problems, particularly in mood- and trauma-related disorders (such as bipolar disorder or depression and post-traumatic stress disorder) where as many as half of people may experience them.

Why do people hear voices?

It is unclear exactly why people hear voices but exposure to prolonged stress, trauma or depression can increase the chances.

Some research suggests people who hear voices might have brains that are “wired” differently, particularly between the hearing and speaking parts of the brain. This may mean parts of our inner speech can be experienced as external voices. So, having the thought “you are useless” when something goes wrong might be experienced as an external person speaking the words.

Other research suggests it may relate to how our brains use past experiences as a template to make sense of and make predictions about the world. Sometimes those templates can be so strong they lead to errors in how we experience what is going on around us, including hearing things our brain is “expecting” rather than what is really happening.

What is clear is that when people tell us they are hearing voices, they really are! Their brain perceives voice experiences as if someone were talking in the room. We could think of this “mistake” as working a bit like being susceptible to common optical tricks or visual illusions.

Coping with hearing voices

When hearing voices is getting in the way of life, treatment guidelines recommend the use of medications. But roughly a third of people will experience ongoing distress. As such, treatment guidelines also recommend the use of psychological therapies such as cognitive behavioural therapy.

The next generation of psychological therapies are beginning to use digital technologies and virtual reality offers a promising new medium.

Avatar therapy allows a person to create a virtual representation of the voice or voices, which looks and sounds like what they are experiencing. This can help people regain power in the “relationship” as they interact with the voice character, supported by a therapist.

Jason’s experience

Aged 53, Jason (not his real name) had struggled with persistent voices since his early 20s. Antipsychotic medication had helped him to some extent over the years, but he was still living with distressing voices. Jason tried out avatar therapy as part of a research trial.

He was initially unable to stand up to the voices, but he slowly gained confidence and tested out different ways of responding to the avatar and voices with his therapist’s support.

Jason became more able to set boundaries, such as not listening to them for periods throughout the day. He also felt more able to challenge what they said and make his own choices.

Over a couple of months, Jason started to experience some breaks from the voices each day and his relationship with them started to change. They were no longer like bullies, but more like critical friends pointing out things he could consider or be aware of.

Gaining recognition

Following promising results overseas and its recommendation by the United Kingdom’s National Institute for Health and Care Excellence, our team has begun adapting the therapy for an Australian context.

We are trialling delivering avatar therapy from our specialist voices clinic via telehealth. We are also testing whether avatar therapy is more effective than the current standard therapy for hearing voices, based on cognitive behavioural therapy.

As only a minority of people with psychosis receive specialist psychological therapy for hearing voices, we hope our trial will support scaling up these new treatments to be available more routinely across the country.

We would like to acknowledge the advice and input of Dr Nadine Keen (consultant clinical psychologist at South London and Maudsley NHS Foundation Trust, UK) on this article.

Leila Jameel, Trial Co-ordinator and Research Therapist, Swinburne University of Technology; Imogen Bell, Senior Research Fellow and Psychologist, The University of Melbourne; Neil Thomas, Professor of Clinical Psychology, Swinburne University of Technology, and Rachel Brand, Senior Lecturer in Clinical Psychology, University of the Sunshine Coast

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