Hacker Newsnew | past | comments | ask | show | jobs | submitlogin
Researchers identify 'switch' to activate cancer cell death (ucdavis.edu)
190 points by DocFeind on Nov 13, 2023 | hide | past | favorite | 77 comments


I know that these kind of write-ups by universities tend to overstate the importance of research. However, it's nice to see a write up that at least on the surface goes into some fairly interesting detail and actually does NOT seem to overstate the significance or imply this will result in a single cure for cancer in just a few easy steps.


It’s nice to read these articles as someone with advanced stage testicular cancer and a 50% 5 year survival. Current treatment is chemo + surgery.

Really appreciate all the smart people in this field. Thank you for the work you do!


You have that 'other' variety I guess? I had the 'good' one (very slow and easy to eradicate after surgery). Hope you will be ok. For me there were no detectable bumps or whatever on the outside, just one day I noticed it was hard as a rock and went to the doctor.

Hope science will find better treatments than chemo (I don't really care about the surgery) and radiation.


Yep mine is weird and rare (PMNSGCT). Starts in the chest cavity, grows to a huge solid tumor. Just finished up 4 cycles of BEP, a very intense chemo regime. But honestly wasn’t too bad. I would do it 10 times over if it means living. Thoracic surgical resection coming up next.


May I ask, how did you find out and how old were you?


I found out at age 29 about 4 months ago. My cancer is rare called PMNSGCT. Presented as large solid tumor in chest the size of a cantaloupe. Symptoms were fevers, night sweats, coughing. They thought it was pneumonia at first. Had a big surprise when I went to the ER lol.


I'm very sorry to hear that! That f*cking sucks! And thank you for sharing. That's something every man should be cautious of. But you say "chest", so checking your balls wouldn't make a difference, right?


Cancer is funky. My dad had lung cancer that travelled to his brain and affected his vision. That's the only way he knew there was something wrong. Well, that and driving a truck and trailer over another truck and trailer.

He went the eye doctor and they said his eyes were healthy. Then they suggested more tests and they found the tumor in his head and the one in his lung.

This also points out why cancer is so dangerous, by the time you realize you have cancer it could have spread around your body. Especially cancer in parts with lots of blood supply or close to lymph nodes.


Sorry to hear that! I really do hope we make advances in cancer detection, that's so fear-inducing that you can't know until it's too late.


Thanks! Luckily my dad is still kicking around, but he was classified stage 4 lung cancer in 2018 (if memory serves) so we understand that's it's going to come back at some point. But he got to see 3 grandbabies since chemo+radiation+surgery so that's precious time he has enjoyed :)


That's a very good reminder that it's not about the years (quantity) but quite definitely how you fill it. So I wish you folks lots of valuable moments and beautiful memories.


Very sorry about your dad. I am so thankful that in my case I still have a shot at cure. People have been telling me I am strong to go through this, but folks like your dad are really the strong ones.


am I missing something? You originally said testicular cancer, now you're describing cancer in the chest.


Many cancer cells travel around the body. The cells may only attach and grow in certain kinds of tissue, but that isn't always the case. At a basic level, cancer is mutated cells...sometimes they mutate more.

I had seminoma testicular cancer. If you must have one, it's what you want. It's very treatable, but also affects the lymphatic system of the body. I had tumors in one testicle and 2 lymph nodes in my abdomen.

Surgery for the testicular tumor, chemo for the others.


sure, but in that case I would expect someone to say cancer rather than specifically testicular cancer.

It's not that important, it just struck me that something was missing in the description.


It is specifically a testicular cancer. The cell type originates in the testicle. It’s a germ cell which are only found in reproductive organs. In my case doctors don’t really know why it “starts in the chest”. Some think it starts in the testes, moves up into the chest and the testes clear up. But there is no definitive science pointing to that. It is very rare. But it is definitely a type of testicular cancer. A rather shitty one unfortunately.


heh, ok. I always assumed testicular cancer meant cancer in the testes, what I'm hearing you say is that it's a type of cancer that starts in the testes so it's considered testicular cancer regardless of where it's found.

that makes sense, thank you for the explanation.


Sometimes it starts in the testes, but in extremely rare cases they believe that it is of primordial origin. For example, when you are developing as an embryo, perhaps the germ cell gets stuck in the chest and takes many years to mutate. But they don’t really know how this works. Very weird stuff.


gotcha, thank you for the education. I wasn't aware that could happen, definitely weird.


I really enjoyed this episode of Peter Attia's podcase: https://peterattiamd.com/keithflaherty2/. They spend a lot of time breaking down the difficulty in cancer treatment, changes over the past decade, the importance of multimodality therapy, and a lot more. A highlight was Attia's analogy to explain antigen presentation.


[not what the article is about, but related topic]

I first heard of dichloroacetic acid about 15 years ago - a cheap drug that also killed cancer cells by allowing mitochondria to induce apoptosis in the cancer cells and not in healthy cells.

https://en.wikipedia.org/wiki/Dichloroacetic_acid#Cancer

It doesn't appear to have gotten a lot of research into what would be a safe dosage, seemingly because it's an old drug that can no longer be patented.


https://cancerquest.org/patients/integrative-oncology/dichlo...

  However, in some systems DCA has been shown to PROTECT cancer cells from death. In research with colon cancer cells, DCA prevented the death of the cells in the laboratory and in animals.28  In mice with neuroblastoma, DCA enhanced the growth of tumor cells.29  Another study showed mixed results: DCA did not slow down tumor growth in mice, though it did make it harder for cancerous cells to spread (metastasize).30


Formulations, therapies, techniques, etc can be patented even if an active ingredient can't be patented. Similarly, modification to structures, prodrugs, etc can be patented, too.


Infuriating. Can we not get public research universities to fund this research???


or even to just research what are non lethal doses, and set it free


It seems like every week there is a new story about some strategy or breakthrough that holds promise to treat or cure cancer, yet we're still stuck with the same treatments, mainly chemo, surgery, and radiation, and generally low survival rates for advanced cancers. Immunotherapy has been hyped for decades yet far from being a cure. Maybe one day it will happen.


My mom was diagnosed with a form of aggressive kidney cancer about 10 years ago that had no really great treatments. Luckily it had not spread (apparently) and they cut out the whole kidney with good success. Until about 4 years ago when it returned, and it had spread to several places. She was going downhill so fast the changes were detectable day-by-day, but they started her on an immunotherapy combination that worked wonders. Gave her about 4 years, as it turns out, she finally succumbed to the cancer a few weeks ago. But it was an amazing four years! And that treatment did not exist when she was originally diagnosed. She'd have been dead years ago if they hadn't been able to buy her enough time for the treatment to become available.

Which is to say, I don't agree with your statement. Cancer treatment has made really great strides and continues to do so.


Sorry to hear that you lost your mom. That 4 years is such a gift though. I lost my sister to a very aggressive ovarian cancer a few years back. Diagnosed and dead within a few months, and she had just had a baby a few months before diagnosis. She didn't make it to his first birthday. Aside from the grief there was just a feeling of such... I know it sounds odd, but "unfairness". Like the whole universe was unfair and wrong. Like there should be a big red button you can push to stop everything and demand a recount. My mom lost her religious faith the day my sister died. My father was, right to the end, certain that something would be done to save her. It was very much a "this isn't happening" moment.

If some treatment had given her 4 years... She'd still be gone by now, and that would still be a tragedy, but she would have had a whale of a time with her boisterous son. He never got to know her. Sure, he would have had to deal with losing his mother. But we all experience love and loss. You can't have one without the other.


Keytruda (pembrolizumab) has been an incredible breakthrough for many cancers. CAR-T therapies have been amazing for non-solid cancers. I personally am hoping to hold on until mRNA cancer vaccines are available via clinical trial (bit more about that towards the bottom of this: https://jakeseliger.com/2023/09/09/life-swallowing-tasting-a...), and there have been incredible early results with them.

Cancer treatments are improving, but with agonizing slowness due to FDA intransigence: https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce....


Hang in there man. Do you feel any better with your latest treatments?


Sorry for your loss!


I’m sorry for your loss. I’m glad you got the extra time! But still… condolences my friend. Losing parents isn’t fun.


>yet we're still stuck with the same treatments, mainly chemo, surgery, and radiation, and generally low survival rates for advanced cancers

Survival rates have been increasing for almost all forms of cancers so fast that it is astounding. Amazing. Stupendous. Heartening.

We've gone from an overall 50% five year survival rate to over 70% in just a couple of decades.

The pancreatic cancer five-year survival rate is very low, but has tripled since 1999.

When I was born you had a 33% chance of living for five more years if you were diagnosed with prostate cancer. Today you have a ~90% chance.

I don't know why people think nothing is changing.


I think it's like voice recognition, which was overhyped in the 90's, then quietly made its way into phone trees, and cars, and now phones so it quietly works everywhere now. I think it used to miss a lot of stuff in the beginning, and that is conflated with missing words occasionally nowadays even though the field has advanced tremendously. which might be analogous to fighting cancer.

I personally know many people who have gotten and then gotten over cancer.


How much of this is due to better detection of cancer? If we discover cancers earlier but still don’t have effective treatment I’d expect the 5-year survival rate to go up even though the actual death day never changed.


which is still fine.

its part of the stack. earlier detection and improved treatments is a very important area.

we still are absolutely failing in preventing those same cancers from reoccuring because we don't know the sequence of triggers or how to prevent them. like, we might know the trigger, but we don't know why one body really becomes more susceptible to them aside from sometimes behavioral or genetic probabilities. hence why we still focus on remission instead of cured, since the body still remains in a state of susceptibility to the same thing and is exposed to the same unknown things, and doesn't revert back to a baseline of not being so.


> its part of the stack. earlier detection and improved treatments is a very important area.

Earlier detection is important but mortality is a better metric than 5-year survival. People tend to conflate the two. If earlier detection doesn't decrease mortality then it's just goosing the 5-year numbers.

This is especially true in geriatric cancers, particularly for example prostate cancers, where most of them are slow growing and not particularly dangerous. You'll outlive the cancer, so knowing about it doesn't mean, well, anything, other than exposing you to risky tests with serious side-effects. Prostate biopsy is really not great.

No-treatment is a great choice in these cases, so really, the detection is all downside, no upside for asymptomatic cases. [1]

[1] https://newsroom.ucla.edu/releases/older-prostate-cancer-pat...


Except we’re spending $50k+ on many of these treatments.


Are you serious? What better way to spend money than on not dying?


A simple question with many different details and answers that won't all fit into a single comment. The two easiest, though:

Which is a better use of 50k? To give one adult one extra year, or the same money to reduce child mortality for a hundred strangers in a different country?

Does the treatment actually reduce mortality, or is it just an expensive placebo?


> Which is a better use of 50k? To give one adult one extra year, or the same money to reduce child mortality for a hundred strangers in a different country?

The answer to that one is very clear: the G7 have more than enough money to fix both extreme poverty (it's just 40 billion $ a year to end hunger [1]) and access to quality medical care (which is a purely USA problem, everyone else has sorted that out decades if not - in the case of Germany - centuries ago) at the same time. There is no need to pit these two issues side-to-side at all.

> Does the treatment actually reduce mortality, or is it just an expensive placebo?

At least for stuff that's not on off-label use, proving efficiency is a mandatory criteria for being allowed to be sold. And some quackery aside, most of the off-label stuff at least has some scientific backing proving that it can actually help.

[1] https://www.wfpusa.org/articles/how-much-would-it-cost-to-en...


> Which is a better use of 50k? To give one adult one extra year, or the same money to reduce child mortality for a hundred strangers in a different country?

Better for whom? Morals are always subjective to your point of view. While points of view of different people sometimes, and even quite often, align with each other enough so that we can talk about shared morals between them, they don't necessary do this all the time. Especially in a scenario of allocation of limited resources.

In the end the only thing that really matters, though, is the point of view of the person who owns these 50k, and nobody else's.


"Which is better" would be a great question if those were the only two things we spent our money on. In reality, both are better than many other ways we spend our money.


This is called the lead time bias - https://en.wikipedia.org/wiki/Lead_time_bias


>We've gone from an overall 50% five year survival rate to over 70% in just a couple of decades.

Has there been a change in actual life expectancy, or does early detection mean that 5 year survival is equivalent to 5-(average years earlier detection) year survival decades ago?


> Has there been a change in actual life expectancy,

Yes!

There’s been a 25% drop in cancer deaths even ignoring differences in demographics. https://www.statista.com/statistics/184566/deaths-by-cancer-...

Back in 1950 it was 193.9 people died of cancer per 100k population, but it was a much younger population. By 1990 216 people died of cancer per 100,000 Americans due to an aging population and possibly lifestyle etc. But it has fallen literally every year since then despite an aging population.

We are down to 146.2 cancer deaths per 100,000 people.


I agree that much is changing in cancer therapy, most promisingly around immunotherapies and other immune related strategies, but the 5 year survival rate change over decades is often attributed to earlier detection as opposed to improved treatments.


> had a 33% chance of living for five more years if you were diagnosed with prostate cancer.

This is patently false. Only late stage prostate cancers are killers. In most cases you catch them early on.


> Only late stage prostate cancers are killers. In most cases you catch them early on.

That doesn't contradict the claim you're replying to.


> I don't know why people think nothing is changing.

It's because people expect a cure the likes of a vaccine, with >95% efficacy.

But it's not entirely their fault, the media all but says "they've cured cancer!" every other day.

When you expect a cure, increasing five year survival rate by 10% falls short.


Maybe mentioning vaccines efficacy is not very on point with the past few years track record


I think people expect cancer cures to be as effective as vaccines really are, while also expecting vaccines (and antibiotics) to be as effective as a Potion of Cure Disease in Skyrim.


I guess people want "real" cure (i.e. a vaccine that makes the cancer fully go away), not just to get couple of extra years of life while puking their brains out on chemo most of that time. Observing how an extended family member and an acquaintance succumbed to cancer in recent years I would agree that the way we treat cancers is still quite barbaric and it sucks immensely for patients.


> we're still stuck with the same treatments

Take a look at CAR T-cell therapy, used for Leukemia and blood cancers (and mentioned in this article). The first trials were happening around 2011, and now there are several FDA-approved therapies using this breakthrough. LLS notes [1]: "In some studies, up to 90 percent of children and adults with B-ALL whose disease had either relapsed multiple times, or failed to respond to standard therapies, achieved remission after receiving CAR T-cell therapy." These are people that would have died 10+ years ago.

My younger brother passed away from ALL in 2012 after a clinical trial for one of these treatments didn't work. His participation in the trial, even with the unsuccessful result, helped further the research that is now saving lives that weren't saved before.

CAR T-cell therapy is perhaps the most powerful breakthrough against blood cancer in history. Now, it might be able to tackle other cancers as well. We're making progress. Of course we all want it to go faster, but it's happening.

1: https://www.lls.org/treatment/types-treatment/immunotherapy/...


I think this is aggressively wrong. First, chemo, surgery, and radiation have advanced dramatically over the years. Chemo is an umbrella term for quite a lot of treatments and isn’t some single drug like Tylenol.

CAR-T has been effective in treating advanced cancers of certain types and solid tumor CAR-T is advancing fast.

Cancer is probably one of the most complex problems we’ve ever tackled with expectation of success. I think it’s considerably harder than quantum computing or other nascent technologies. Further I think we are building fundamental understandings of life itself that leads to enormous adjacent benefits, most especially in aging and longevity.

It’s also not a single disease. It’s a description of a behavior of cells in the body that leads to certain outcomes. The causes, mechanisms, etc, are all specific to the cell types, of which there are many, the individual, and random chance. That makes the problem domain almost infinitely complex, so finding a way through it is hard already. But add onto it that cancer cells are you eliminating them without eliminating you is absurdly hard, and leaving even a small number behind risks a relapse that is resistant to the prior treatments because a few cells happened to have a random mutation that protected them.

All this said, I think cancer treatment will be a domino effect discovery. We will slog along reading these elusive yet promising articles until one day, we have done enough of the discovery and exploration, and things will be very different very quickly. Similar to AI - I wouldn’t have predicted generative AI would have effectively solved NLP two years ago, despite tons of promising headlines and articles for the last 50 years.


One aspect of the problem in talking about "cancer" is that we're talking about a large collection of diseases, not a singular disease or phenomenon:

> cancer is actually an umbrella term for scores of different diseases—each with its own unique characteristics and, often, unique treatment needs

https://www.cancercenter.com/community/blog/2023/10/cancer-i...

So every time I read a headline about a new cancer treatment, I think of it as chipping away at one small rock in a giant field of rocks that we're trying to turn into dust. The university "public affairs" (PR) department may talk about about that small rock as if it were all rocks or all one big rock, and as if the chip was a giant blow. PR people talk like that because their job isn't to convey truth; the PR job is to generate news buzz for the university. So unless you have the time and energy to read those papers, it's best to ignore what the PR people say and just to imagine that picture.


Anecdata, but I personally know three people who've been given an extra 5+ years each due to recent developments in cancer treatments (better chemo, to be fair), and I'm not exactly a social butterfly.

Not a miracle, but not nothing.


Those things are happening. However it is a decade at best from something in a lab to something in general use. That is at best, quite often things work in a lab, but don't work in the real world. sometimes not work means it works, but the side effects are worse than current treatments (or even worse than doing nothing!) Sometimes it works on a sub group of people and we need more time to figure out who/why it works on and then target those people.

if you look at day to day or even year to year it looks like things are not moving. However if you look at decades things have gotten much better.


> yet we're still stuck with the same treatments, mainly chemo, surgery, and radiation, and generally low survival rates for advanced cancers.

I disagree. Growing up in my teens that was certainly true, but my fathers been battling stage 4 prostate cancer for a little over a decade and had few if any side effects from the treatments. There is a whole line of targeted chemotherapies you can take one after another after another when one stops being effective. On the other hand this can be perceived as a slow march to death from the flu eventually. It was stated to him ten years ago that he likely won't die from cancer. He's now on the last medication he will likely take, which addresses pancreatic cancer that is derived from prostate cancer.

What I will argue is archaic is how long his doctor ignored rising PSA levels due to some magical number that the insurance company would not act before. At that time, the only route he had was removal of his entire prostate which causes a lot of quality of life issues. Since then they've developed more targeted treatments but I don't know that they're training family practitioners adequately yet still.


Stage 4 melanoma used to mean you'd be dead in a year. I personally know someone who was flat-out cured of stage 4 melanoma.

Her only treatment was three doses of immunotherapy. Her tumors shrank by two-thirds almost immediately. For the next seven years they just monitored, and finally they declared her cancer-free. She doesn't even have to go in for scans anymore.


She should go for scans anyway. Celebrate the victory every year.


Nah, she probably has some genetic damage already that lead up to that cancer. CT scans are 70x more radiation than X-Rays and contribute to lifetime cancer risk.


MRI? No radiation.


We have made huge progress in a relatively short amount of time. Cancer has been difficult to cure for three reasons:

- Cancerous cells are very similar to non-cancerous cells, and hard to target without harming the rest of the body

- If one treatment is unsuccessful, cancer can adapt by mutating to bypass your attempt.

- Cancer isn't a single disease. It is thousands of diseases with a similar outcome: uncontrolled growth with invasion. You really have to understand the entire signaling pathway and the various tumor suppressor genes / oncogenes in order to understand all the many ways cell replication can go wrong.

Even within a single classification (say, breast cancer) you have HER2+ breast cancer (which has an overdensity of RTK leading to growth factor independence), estrogen receptor+ breast cancer, and others, all of which require a different treatment approach, and the cancer can adapt by mutating further down the growth factor signaling pathway if you attack it in one place.


Immunotherapy has come along and shown promise - I know someone who is still alive almost 15 years later who initially presented with metastatic melanoma.


Things are moving though. My mum spent a day on a machine that filtered out stem cells from her blood, that were donated to her brother to rebuild his immune system. The old treatment was a much more invasive bone marrow transplant, IIRC.


Look at the incentives. To get funding for research, it's easier if you have prior research that supports your proposal. Hence a lot of stuff gets written up in very optimistic terms, to help get more funding to continue the research. It doesn't seem to matter that none of it really works in the end. It's also the reason people don't publish failed projects, even though from a science perspective those might be helpful to identify dead ends.


Anyone know of any breakthroughs in treating peritoneal mesothelioma?


Switch to life 8)


[flagged]


Is the content of the article not exactly what the headline says?


It is not.

As a simplified analogy, the title is saying "we identified this lock on the cells", while actually the "lock" has been known for a long time and what they identified was a possible "key" that might fit, but they haven't actually done it yet.


So have cancer cells... in fact I believe that's the problem.


Cell division is imperfect, pretty much impossible to avoid mutation and loss over the lifetime of an organism. This compounds over time and is the reason most cancers are later in life


Many animals seem resistance to cancer. Including big animals like whales where you'd think if was simply statistics on cell division they would be more likely to get cancer.


Some studies indicated this resistance was tied to the amount of redundancy in DNA. https://elifesciences.org/articles/21864 talks about how elephants have 20 versions of the tumor suppressor gene TP53. So it is statistics, and some animals evolved defenses.


But size/height does play a role in humans. For example, shorter people tend to live longer average lifespans.[1]

[1] https://pubmed.ncbi.nlm.nih.gov/12586217/


they seem to have evolved a defense against tumors to quell the growth, but can still get it, and through some skimming of research, it seems to show that most species end up with the same amount of mutations by end of life, so adjusted for different lifespans, or different mutation rates per species




Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact

Search: