Premenstrual dysphoric disorder, gamifying exercise, improving cancer drug trials, and repurposing a psoriasis drug for osteosarcoma?
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What is the focus of today’s Health Report episode?
This is an ABC podcast.
Hello and welcome to this week's health report with me, Norman Swan. Today, the lack of evidence of improved survival and quality of life benefits behind many new and expensive cancer medications. How best to design apps which will make our behavior healthier, premenstrual dysphoric disorder, it's not a myth, and how a search for cancer genes in the heart-treat form of cancer called sarcoma may lead to an unexpected life-saving use for a medication which was originally designed to treat psoriasis. The insight came from research at the Garvin Institute in Sydney into what looks like an Achilles heel in some forms of cancer. David Thomas is head of the cancer research program at the Garvin. Welcome back to the Health Report, David.
It's nice to be here, Norman. Just explain what sarcoma is, remind us.
Yes, so sarcomas are um rare cancers of the connective tissue, muscle, fat, bone, and cartilage. And they particularly affect a young population. They're very uncommon and their cure rates are something around sixty percent. So we lose forty percent of our patients to the disease. And surgery is still the focus of treatment. It's absolutely essential. And then we add chemotherapy and radiotherapy on top of that. So
it
doesn't but it doesn't.
Now just w we need to just a little bit of history, I'm not a lot of time, but a little bit of history because the Americans did this sort of General gene search in sarcoma to look at what lit up. And they found this one gene, but it wasn't a cancer gene.
No, it was unexpected. Um it's a gene called GRM4, which none of us had ever heard of, and that sent us to the books and we found that it was associated with inflammation and that piqued our interest. And
what's the connection?
You picked it up a few years ago. Yes, that's right. So um our first job was to try and figure out a way of verifying whether or not this very large genome-wide association study was true. So we Which is really a a dragnet for genes. It is. And it often turns up false positives, which is why we were so obsessive about it. We generated a mouse uh which lacked GRM4, and uh that confirmed that the tumors developed more quickly. when mice lacked the gene, which implied that it had a causal role. And then um there'd been some studies recently um suggesting that germ 4 regulated inflammation in the central nervous system in another mouse study. And that got our interest because immunotherapies, as you know, target the immune system.
So that's cancer c cancer the cancer immunotherapies? Yes, exactly.
And ha you came across this immune molecule that seemed to be involved?
Yeah, so central amongst the molecules that GRM4 regulated is the gene interleukin-23 or IL-23. And uh interleukin-23 uh we also put into our mouse model, and those mice were astonishingly protected from tumor development. Normally when we knock out a gene in the immune system, the tumors develop more quickly 'cause we impair the immune system's ability to eradicate the tumors, but this had the opposite effect. We were actually retarded. In fact, about eighty percent of the mice did not go on to develop tumour.
And these are mice that were prone to developing the tumor. Yes. But I thought that you what you also found, so I'm getting confused now, but you know you'll I'm sure you'll clarify it for me, is that when because not everything that happens in mice happens in humans.
How does the Garvan Institute’s research link the GRM4 gene to osteosarcoma?
That's right. And you and you looked at human samples of osteosauri.
Yeah, so that was another piece of data that added to the puzzle. When we looked at interleukin twenty three levels in human cancers, including in sarcomas, they were generally higher than the surrounding tissue. So it seemed to be associated with tumor development. The opposite from what you found in the mice. No, exactly what you would expect from the mouse. So when we knocked out interleukin twenty three in the mice, they were protected. They used interleukin twenty three to it was uh something we haven't seen. So Right. It's an unusual thing to observe.
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Chapters
8 chapters
1
What is the focus of today’s Health Report episode?
0:02–3:17
2
How does the Garvan Institute’s research link the GRM4 gene to osteosarcoma?
3:17–7:22
3
Why could a psoriasis drug become a new treatment for bone‑cancer patients?
7:22–11:49
4
What evidence shows that many new cancer medicines lack survival benefit?
11:49–16:19
5
How is Premenstrual Dysphoric Disorder (PMDD) defined and diagnosed?
16:19–20:24
6
What treatment options are available for women with severe PMDD?
20:24–23:51
7
How does gamifying exercise with competition improve long‑term step counts?
23:51–27:42
8
What are the broader implications of gamified health programs for workplaces and insurers?
27:42–28:36
Speakers
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