Drug trio found to block tumour resistance in pancreatic cancer

> Clinical implications: While more research will be needed before trials in humans can begin

Why? Seriously, think about it. Most people with pancreatic cancer have nothing to lose and many of them have just weeks or months to live.

Daraxonrasib, Afatinib, and SD36 are molecules that can already be purchased in bulk, and what's the worst that can happen?

Our society's morbid, irrational fear of quack medicine causes orders of magnitude more deaths through therapeutic neglect than it prevents through safety screening. "Better 10,000 die of cancer than 1 person die of fraud/waste/mismanagement or even in failed experiments performed in good faith."

IN MICE. (To be fair, also IN SOME OTHER BETTER MICE).

https://jamesheathers.medium.com/in-mice-explained-77b61b598...

(mostly a joke, but I'd be in favor of adding context to the HN headline if possible)

Recently YouTube again started recommending to me channels of people who died of cancer.

I looked at a clip of a man just a few years my senior where he was describing the symptoms that in his view should have made him go see a doctor earlier, because maybe then his pancreatic cancer wouldn't have been fatal.

Truth be told they wouldn't raise any red flags if I had them.

Only thing that I'm doing differently is having blood tests done on an annual basis, but those only show anything when e.g. the cancer has spread to the liver, which is typically too late anyway. It's an incredibly insidious disease, and if the tumor is growing on the wrong end of the organ, it won't give any symptoms whatsoever.

I've been playing to much pokemon with my kids, read this as "Dugtrio"

As we are always starting with mice, I am wondering if there are some drug that could work on humans but not on mice.

Am I misunderstanding the headline? Is the word "block" now meaning "enhance" instead of "stop"? I would think based on the text of the article that it enhances resistance. Or are tumors necessary to stop cancer growth (even though it is cancer growth?)

For all the folks complaining about "it's only in mice! things never work in humans!" -- I work at MSK and we definitely have seen success treating PDAC in humans: https://www.nature.com/articles/s41586-023-06063-y

"Why don't I see these treatments hitting the general public?" Because trials like these are phase I/II. Then you need a phase III that takes a long time to recruit a large cohort and has overall survival as an end point so you need a long time to measure the actual outcome you care about. And most trials fail in phase III because the surrogate end points used in phase II studies, like progression free survival (ie how long did patients go before their disease advanced in screens), are not necessarily great predictors of improved overall survival.

Specifically for cancer vaccines, this paper was a driving force behind MSK establishing a cancer vaccine center to scale up these personalized neoantigen mRNA vaccines. It's very very difficult to do and extremely expensive right now.

I keep reading about these advancements in pancreatic cancer like early detection or possible treatments, but nothing ever seems to make it to daylight. Is there a reason why there's such disparity between this?

if that holds true in humans that would be a huge win. but it would be interesting at which stage those drugs still help. btw, it is said Chris Rea was diagnosed with pancreatic cancer at the age of 33, he died last year at he age of 74. it would be interesting to know what circumstance helped him to fight the cancer for such a long time

It's funny how many years of "X found to be effective in fighting cancer" stories have filtered through HN and then you never hear about it again.

The research at treating mouse cancer has been making great strides--people cancer still has a long way to go though.

> These agents together were tested in orthotopic mouse models of PDAC, where tumour cells are implanted in a location that closely resembles their natural environment in the pancreas.

Ugh, of course: "in mice"!

> The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice, known as patient-derived tumour xenografts (PDX).

OK, maybe "in human tissue grown in mice" isn't so bad.

Fingers crossed. Pancreatic cancer is terrible.

I was wondering what preclinical models meant. It would be more accurate to call it animal models. I read roughly 3% - 5% of compounds move from preclinical cancer therapies to fda approval. That’s a tough success rate.

At usual baity headline. It's in rat, it's on a tumor model, so there is a good chance it's like the other thousands mice studies that do not replicate on humans

Anybody read that as "Dugtrio found to block tumour resistance..."?

"Here we describe peptides secreted as part of the Diglett evolution process, that have been found to disrupt oncocyte metabolism in vitro..."

This should be seen as a warning of how much time and efforts and money and stability are required to cultivate a discovery that could have never happened.

Spanish researcher from Madrid. Hired by US on a grant. Worked hard and became director of the Oncology department on the NCI on Maryland. Somebody on the Spanish government decided to bet strong on him and recover it for Spanish Cancer research. A specific customised job offer was created for him. Politicians came and go; some are sensitive about science, other not so much. Some promises were never fulfilled, and he was about to quit and migrate again until private companies stepped on the scene with the resources needed and the will to allocate those resources. Money well spent, that was about to never find his target.

Nobel prizes were created exactly for this kind of humble, serious, zero-nonsense, zero-drama, all-work scientists.

The question here is: how much "Barbacids" quit US in the last year? Scientists aren't stupid. Everybody is aware that Barbacid in US today would have being harassed just for speaking Spanish and having a scarred face. All points that US is bleeding talent at a level never seen in their history.

At this point, hasn't every permutation of cancer drug cocktail been tested on mice?

> The results demonstrated the therapy not only reduced tumour size but also entirely stopped tumour growth with no evidence of tumour resistance for more than 200 days after treatment.

More details in https://www.pnas.org/doi/suppl/10.1073/pnas.2523039122/suppl... See page 25

In mice, N=12.

1 survived 200 days without cancer and was euthanized for 'ocular ulcers'.

5 survived 50-150 days, without cancer but were euthanized for other health problems

6 survived 50-150 days, and still had a smaller tumor and were euthanized for other health problems

My take away: Interesting, but the press article is overselling the result by a lot.

Edit: Fixed link.