From immunotherapy to mRNA vaccines – the latest science on melanoma treatment explained
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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.
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The Couple’s Guide to Thriving with ADHD – by Melissa Orlov and Nancie Kohlenberger
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ADHD (what a misleadingly-named condition) is most often undiagnosed in adults, especially older adults, and has far-reaching effects. This book explores those!
Oftentimes ADHD is not a deficit of attention, it’s just a lack of choice about where one’s attention goes. And the H? It’s mostly not what people think it is. The diagnostic criteria have moved far beyond the original name.
But in a marriage, ADHD symptoms such as wandering attention, forgetfulness, impulsiveness, and a focus on the “now” to the point of losing sight of the big picture (the forgotten past and the unplanned future), can cause conflict.
The authors write in a way that is intended for the ADHD and/or non-ADHD partner to read, and ideally, for both to read.
They shine light on why people with or without ADHD tend towards (or away from) certain behaviours, what miscommunications can arise, and how to smooth them over.
Best of all, an integrated plan for getting you both on the same page, so that you can tackle anything that arises, as the diverse team (with quite different individual strengths) that you are.
Bottom line: if you or a loved one has ADHD symptoms, this book can help you navigate and untangle what can otherwise sometimes get a little messy.
Click here to check out The Couple’s Guide to Thriving with ADHD, and learn how to do just that!
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Clean Needles Save Lives. In Some States, They Might Not Be Legal.
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Kim Botteicher hardly thinks of herself as a criminal.
On the main floor of a former Catholic church in Bolivar, Pennsylvania, Botteicher runs a flower shop and cafe.
In the former church’s basement, she also operates a nonprofit organization focused on helping people caught up in the drug epidemic get back on their feet.
The nonprofit, FAVOR ~ Western PA, sits in a rural pocket of the Allegheny Mountains east of Pittsburgh. Her organization’s home county of Westmoreland has seen roughly 100 or more drug overdose deaths each year for the past several years, the majority involving fentanyl.
Thousands more residents in the region have been touched by the scourge of addiction, which is where Botteicher comes in.
She helps people find housing, jobs, and health care, and works with families by running support groups and explaining that substance use disorder is a disease, not a moral failing.
But she has also talked publicly about how she has made sterile syringes available to people who use drugs.
“When that person comes in the door,” she said, “if they are covered with abscesses because they have been using needles that are dirty, or they’ve been sharing needles — maybe they’ve got hep C — we see that as, ‘OK, this is our first step.’”
Studies have identified public health benefits associated with syringe exchange services. The Centers for Disease Control and Prevention says these programs reduce HIV and hepatitis C infections, and that new users of the programs are more likely to enter drug treatment and more likely to stop using drugs than nonparticipants.
This harm-reduction strategy is supported by leading health groups, such as the American Medical Association, the World Health Organization, and the International AIDS Society.
But providing clean syringes could put Botteicher in legal danger. Under Pennsylvania law, it’s a misdemeanor to distribute drug paraphernalia. The state’s definition includes hypodermic syringes, needles, and other objects used for injecting banned drugs. Pennsylvania is one of 12 states that do not implicitly or explicitly authorize syringe services programs through statute or regulation, according to a 2023 analysis. A few of those states, but not Pennsylvania, either don’t have a state drug paraphernalia law or don’t include syringes in it.
Those working on the front lines of the opioid epidemic, like Botteicher, say a reexamination of Pennsylvania’s law is long overdue.
There’s an urgency to the issue as well: Billions of dollars have begun flowing into Pennsylvania and other states from legal settlements with companies over their role in the opioid epidemic, and syringe services are among the eligible interventions that could be supported by that money.
The opioid settlements reached between drug companies and distributors and a coalition of state attorneys general included a list of recommendations for spending the money. Expanding syringe services is listed as one of the core strategies.
But in Pennsylvania, where 5,158 people died from a drug overdose in 2022, the state’s drug paraphernalia law stands in the way.
Concerns over Botteicher’s work with syringe services recently led Westmoreland County officials to cancel an allocation of $150,000 in opioid settlement funds they had previously approved for her organization. County Commissioner Douglas Chew defended the decision by saying the county “is very risk averse.”
Botteicher said her organization had planned to use the money to hire additional recovery specialists, not on syringes. Supporters of syringe services point to the cancellation of funding as evidence of the need to change state law, especially given the recommendations of settlement documents.
“It’s just a huge inconsistency,” said Zoe Soslow, who leads overdose prevention work in Pennsylvania for the public health organization Vital Strategies. “It’s causing a lot of confusion.”
Though sterile syringes can be purchased from pharmacies without a prescription, handing out free ones to make drug use safer is generally considered illegal — or at least in a legal gray area — in most of the state. In Pennsylvania’s two largest cities, Philadelphia and Pittsburgh, officials have used local health powers to provide legal protection to people who operate syringe services programs.
Even so, in Philadelphia, Mayor Cherelle Parker, who took office in January, has made it clear she opposes using opioid settlement money, or any city funds, to pay for the distribution of clean needles, The Philadelphia Inquirer has reported. Parker’s position signals a major shift in that city’s approach to the opioid epidemic.
On the other side of the state, opioid settlement funds have had a big effect for Prevention Point Pittsburgh, a harm reduction organization. Allegheny County reported spending or committing $325,000 in settlement money as of the end of last year to support the organization’s work with sterile syringes and other supplies for safer drug use.
“It was absolutely incredible to not have to fundraise every single dollar for the supplies that go out,” said Prevention Point’s executive director, Aaron Arnold. “It takes a lot of energy. It pulls away from actual delivery of services when you’re constantly having to find out, ‘Do we have enough money to even purchase the supplies that we want to distribute?’”
In parts of Pennsylvania that lack these legal protections, people sometimes operate underground syringe programs.
The Pennsylvania law banning drug paraphernalia was never intended to apply to syringe services, according to Scott Burris, director of the Center for Public Health Law Research at Temple University. But there have not been court cases in Pennsylvania to clarify the issue, and the failure of the legislature to act creates a chilling effect, he said.
Carla Sofronski, executive director of the Pennsylvania Harm Reduction Network, said she was not aware of anyone having faced criminal charges for operating syringe services in the state, but she noted the threat hangs over people who do and that they are taking a “great risk.”
In 2016, the CDC flagged three Pennsylvania counties — Cambria, Crawford, and Luzerne — among 220 counties nationwide in an assessment of communities potentially vulnerable to the rapid spread of HIV and to new or continuing high rates of hepatitis C infections among people who inject drugs.
Kate Favata, a resident of Luzerne County, said she started using heroin in her late teens and wouldn’t be alive today if it weren’t for the support and community she found at a syringe services program in Philadelphia.
“It kind of just made me feel like I was in a safe space. And I don’t really know if there was like a come-to-God moment or come-to-Jesus moment,” she said. “I just wanted better.”
Favata is now in long-term recovery and works for a medication-assisted treatment program.
At clinics in Cambria and Somerset Counties, Highlands Health provides free or low-cost medical care. Despite the legal risk, the organization has operated a syringe program for several years, while also testing patients for infectious diseases, distributing overdose reversal medication, and offering recovery options.
Rosalie Danchanko, Highlands Health’s executive director, said she hopes opioid settlement money can eventually support her organization.
“Why shouldn’t that wealth be spread around for all organizations that are working with people affected by the opioid problem?” she asked.
In February, legislation to legalize syringe services in Pennsylvania was approved by a committee and has moved forward. The administration of Gov. Josh Shapiro, a Democrat, supports the legislation. But it faces an uncertain future in the full legislature, in which Democrats have a narrow majority in the House and Republicans control the Senate.
One of the bill’s lead sponsors, state Rep. Jim Struzzi, hasn’t always supported syringe services. But the Republican from western Pennsylvania said that since his brother died from a drug overdose in 2014, he has come to better understand the nature of addiction.
In the committee vote, nearly all of Struzzi’s Republican colleagues opposed the bill. State Rep. Paul Schemel said authorizing the “very instrumentality of abuse” crossed a line for him and “would be enabling an evil.”
After the vote, Struzzi said he wanted to build more bipartisan support. He noted that some of his own skepticism about the programs eased only after he visited Prevention Point Pittsburgh and saw how workers do more than just hand out syringes. These types of programs connect people to resources — overdose reversal medication, wound care, substance use treatment — that can save lives and lead to recovery.
“A lot of these people are … desperate. They’re alone. They’re afraid. And these programs bring them into someone who cares,” Struzzi said. “And that, to me, is a step in the right direction.”
At her nonprofit in western Pennsylvania, Botteicher is hoping lawmakers take action.
“If it’s something that’s going to help someone, then why is it illegal?” she said. “It just doesn’t make any sense to me.”
This story was co-reported by WESA Public Radio and Spotlight PA, an independent, nonpartisan, and nonprofit newsroom producing investigative and public-service journalism that holds power to account and drives positive change in Pennsylvania.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
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Tooth Remineralization: How To Heal Your Teeth Naturally
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Dr. Michelle Jorgensen, dentist, explains:
The bare-bones details:
Teeth cannot be regrown (yet!) but can be remineralized, which simply involves restoring lost minerals. When we’re talking about health, “minerals” is usually used to mean elemental minerals, like calcium, magnesium, phosphorus, etc, but the specific mineral that’s needed here is hydroxyapatite (a calcium phosphate mineral, the same as is found in bones).
Not only can acids from food and bacteria dissolve the minerals from the teeth, but also, the body itself may extract minerals from the teeth if it needs them for other functions it considers more critical and/or more urgent.
Cavities occur when acids create porous holes in teeth by dissolving minerals, which allows bacteria to invade, which means more acid, and cavities.
Remineralization can be achieved by doing the following things:
- Use hydroxyapatite-based products (tooth powder, mouthwash).
- Improve gut health to ensure proper mineral absorption.
- Reduce acidic food and drink intake.
- Maintain good oral hygiene to prevent bacteria build-up.
- Eat foods rich in vitamins A, D, E, and K, which help direct minerals to teeth and bones.
For more on all of the above, enjoy:
Click Here If The Embedded Video Doesn’t Load Automatically!
Want to learn more?
You might also like to read:
- Less Common Oral Hygiene Options
- Fluoride Toothpaste vs Non-Fluoride Toothpaste – Which is Healthier?
Take care!
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Related Posts
Breathe; Don’t Vent (At Least In The Moment)
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Zen And The Art Of Breaking Things
We’ve talked before about identifying emotions and the importance of being able to express them:
Answering The Most Difficult Question: How Are You?
However, there can be a difference between “expressing how we feel” and “being possessed by how we feel and bulldozing everything in our path”
…which is, of course, primarily a problem in the case of anger—and by extension, emotions that are often contemporaneous with anger, such as jealousy, shame, fear, etc.
How much feeling is too much?
While this is in large part a subjective matter, clinically speaking the key question is generally: is it adversely affecting daily life to the point of being a problem?
For example, if you have to spend half an hour every day actively managing a certain emotion, that’s probably indicative of something unusual, but “unusual” is not inherently bad. If you’re managing it safely and in a way that doesn’t negatively affect the rest of your life, then that is generally considered fine, unless you feel otherwise about it.
A good example of this is complicated grief and/or prolonged grief.
But what about when it comes to anger? How much is ok?
When it comes to those around you, any amount of anger can seem like too much. Anger often makes us short-tempered even with people who are not the object of our anger, and it rarely brings out the best in us.
We can express our feelings in non-aggressive ways, for example:
and
Seriously Useful Communication Skills!
Sometimes, there’s another way though…
Breathe; don’t vent
That’s a great headline, but we can’t take the credit for it, because it came from:
Breathe, don’t vent: turning down the heat is key to managing anger
…in which it was found that, by all available metrics, the popular wisdom of “getting it off your chest” doesn’t necessarily stand up to scrutiny, at least in the short term:
❝The work was inspired in part by the rising popularity of rage rooms that promote smashing things (such as glass, plates and electronics) to work through angry feelings.
I wanted to debunk the whole theory of expressing anger as a way of coping with it,” she said. “We wanted to show that reducing arousal, and actually the physiological aspect of it, is really important.❞
And indeed, he and his team did find that various arousal-increasing activities (such as hitting a punchbag, breaking things, doing vigorous exercise) did not help as much as arousal-decreasing activities, such as mindfulness-based relaxation techniques.
If you’d like to read the full paper, then so would we, but we couldn’t get full access to this one yet. However, the abstract includes representative statistics, so that’s worth a once-over:
Caveat!
Did you notice the small gap between their results and their conclusion?
In a lab or similar short-term observational setting, their recommendation is clearly correct.
However, if the source of your anger is something chronic and persistent, it could well be that calming down without addressing the actual cause is just “kicking the can down the road”, and will still have to actually be dealt with eventually.
So, while “here be science”, it’s not a mandate for necessarily suffering in silence. It’s more about being mindful about how we go about tackling our anger.
As for a primer on mindfulness, feel free to check out:
No-Frills, Evidence-Based Mindfulness
Take care!
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The Well Plated Cookbook – by Erin Clarke
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Clarke’s focus here is on what she calls “stealthy healthy”, with the idea of dishes that feel indulgent while being great for the health.
The recipes, of which there are well over 100, are indeed delicious and easy to make without being oversimplified, and since she encourages the use of in-season ingredients, many recipes come with a “market swaps” substitution guide, to make each recipe seasonal.
The book is largely not vegetarian, let alone vegan, but the required substitutions will be second-nature to any seasoned vegetarian or vegan. Indeed, “skip the meat sometimes” is one of the advices she offers near the beginning of the book, in the category of tips to make things even healthier.
Bottom line: if you want to add dishes to your repertoire that are great for entertaining and still super-healthy, this book will be a fine addition to your collection.
Click here to check out The Well Plated Cookbook, and get cooking!
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Which Bell Peppers To Pick?
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Bell Peppers: A Spectrum Of Specialties
We were going to do this as part of our ongoing “This Or That?” challenge, but as there are four main types all with many different benefits, we thought this bunch of fruits deserved a main feature.
And yes, they’re botanically fruits, even if culinarily used as vegetables—much like tomatoes, famously!
They’re all the same (but also very much not)
A thing to know is that whether bell peppers be green, yellow, orange, or red, they’re all the same plant, Capiscum anuum. All that differs is how early or late they’re harvested.
Notwithstanding the “Capiscum” genus, they don’t contain capsaicin (as is found in hot peppers). Capsaicin’s a wonderful phytochemical:
Capsaicin For Weight Loss And Against Inflammation
…but today we’re all about the bell peppers.
So, let’s see how they stack up!
💚 Green for lutein
Lutein is especially important for the eyes and [the rest of the] brain, to the point that there’s now an Alzheimer’s test that measures lutein concentration in the eye:
Green peppers have most of this important carotenoid, though the others all have some too. See also:
💛 Yellow for vitamin C
Yellow peppers are technically highest in vitamin C, but all of them contain far more than the daily dose per fruit already, so if there’s any color of pepper that’s nutritionally the most expendable, it’s yellow, since any other color pepper can take its place.
Watch out, though! Cooking destroys vitamin C, so if you want to get your Cs in, you’re going to want to do it raw.
🧡 Orange for zeaxanthin and cryptoxanthins
Similar in their benefits to lutein, these antioxidant carotenoids are found most generously in orange peppers (20x as much as in yellow, 10x as much as in red, and slightly more than in green).
❤️ Red for vitamins A & B6
Red peppers are richest by far in vitamin A, with one fruit giving the daily dose already. The others have about 10% of that, give or take.
Red peppers also have the most vitamin B6, though the others also have nearly as much.
❤️ Red for lycopene
We must do a main feature for lycopene sometime, as unlike a lot of antioxidant carotenoids, lycopene is found in comparatively very few foods (most famously it’s present in tomatoes).
Red is the only color of pepper to have lycopene.
10almonds tip: to get the most out of your lycopene, cook these ones!
Lycopene becomes 4x more bioavailable when cooked:
Lycopene in tomatoes: chemical and physical properties affected by food processing ← this paper is about tomatoes but lycopene is lycopene and this applies to the lycopene in red peppers, too
And the overall winner is…
You! Because you get to eat all four of them
Enjoy!
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