Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma

They thought too much sun was bad for you because back then tanned skin was considering a mark of being poor and pale skin was a mark of being wealthy since rich people didn’t have to work outside.

They also had puritanical Victorian notions of modesty and covering up.

There was no knowledge linking sun exposure to cancer or negative health effects. People in the past indeed were ignorant on many things.

So it's not that they ignored the all knowledge. I blame most of it on the rather detrimental tech advancement. Like cigarettes with filters: now safer (except you can smoke more now, and the cancer risk is still a disaster)

I’d be curious to know if tetraethyllead in gasoline has anything to do with people from that time being cavalier about exposure to the sun, or if the science was just not there to make the connection between sun exposure and skin cancer.

We never wore sunscreen as kids because we didn't burn. I probably have had three sunburns in my life. Learned once I became an adult that that wasn't sound logic...

However, I’ve never gotten so much as a whisper of sunburn / suntan / anything on an actually cloudy day where sun wasn’t hitting me directly. Is the damage a different type that’s imperceptible? Or is this a public health comms strategy where they assume people will see a single cloud in the sky and decide it’s fine to skip sunscreen, so they talk about how you should slather yourself with sunscreen 24/7, even if the sun is obscured?

From https://onlinelibrary.wiley.com/doi/10.1002/ijc.35463

> Cutaneous melanoma (CM) accounted for around 331,700 cancer cases globally in 2022

> An estimated 267,353 (95% uncertainty intervals [UI]: 242,818, 278,638) CM cases were UVR attributable globally in 2022

UVR = Ultraviolet radiation

Cutaneous melanoma (CM) is the vast majority of melanoma cases in the US at least:

> The percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, from https://pubmed.ncbi.nlm.nih.gov/9781962/

tl;dr ~80% of Cutaneous melanoma cases are attributable to UV exposure.

So this should answer the question of "how much better is this with the best we currently have".

https://archive.ph/SQQ97

Buddy, this is a phase 3 trial. This is about as close as you can get to "anything that can be used on patients" without already being approved.

It is clear that you don't have experience in this area.

Moderna used a simple heuristic, "how likely is this antigen to show up on the cell surface?" which makes sense, since an antigen has to show up on the cell surface for the immune system to see it. But there's so much missing from this model, and we just don't have enough data. Failures in clinical trials of mRNA vaccines may well be caused by this problem. (Yes, this is a good problem for AI, if we can get enough data).

"Almost never" is doing a lot of work. You may be aware that most drugs fail over the course of development and human trials?

Anyway, checkpoint inhibitor therapy is a massive boon to oncology and was only brought into widespread use over the past 15 years.

Those few exceptions have been monumental in how they've changed cancer treatment. Skin cancer has been particularly well treated with immunotherapy, but other cancers have also benefited from the exact same research and drugs (as it turns out, the specific mutations the immunotherapies like Keytruda target express in other cancers). The reason skin cancer gets so much attention is because it's one of the most commonly diagnosed and treated cancers. (Colon is more common, I believe, but it often doesn't get detected. Get your colonoscopies folks).

It has moved fast enough that I've heard from multiple oncologists that the all 5 year survivability numbers are dated because the treatments are newer than the studies.

We've come a LONG way in a very short period in terms of cancer treatment. It still sucks, but not as much as it once did.