A Universal Cancer Treatment?
nautil.us
nautil.us
However, in recent years, a very effective checkpoint inhibitor immunotherapy has been developed for the cancer in question. ~2x the success rates of traditional chemo, greatly increased overall survival statistics, and with massively reduced side effects. The results speak for themselves: this drug has granted my relative years of extra life in the worst case, and a path to a deep, long remission in the best case.
I think that as the technology develops, by 2040 we'll be looking back at the present state of the art with the same incredulity that we currently have for, like, bloodletting with leeches in the Middle Ages. I think they've been saying this for a long time now, but it's truer than ever that a real cure for cancer is right around the corner.
YMMV.
One thing to remember is that "Lung Cancer" is not just one thing. There are mutations of different genes, there are overexpressions of different genes. Each one has its own new medicines. Also, some peoples' cancers are more aggressive than others, and while for many they can find the right drug, for some nothing works.
Keytruda works wonders for some. It did not for me. I had 4 treatments of the CPP (carboplatin, pemetrexed, and pembrolizumab) triad, which had some success. They then put you on "maintenance," which is the PP without the carboplatin (which is the really old school platinum-based chemo). Maintenance did nothing for me. My main tumor grew more than 50% in 2 months.
Last summer I started 9 months on a chemo/immuno that was geared towards my specific mutation. It actually did wonders. It resulted in a 98% shrinkage of my main tumor before I ended up with pneumonitis from it and had to stop. But I've been able to be off treatment for the entire summer. I know there are others who have tried this, and it didn't work.
So yeah, I'm really, really glad your relative was able to get some relief from the Keytruda. But I also wish it were the wonder cure for everyone that it was for them.
The process is grueling in hindsight, but I'm glad to hear you're getting results. At first I would have said "if this is going to kill me, make it sooner rather than later" to avoid a drawn-out painful experience, but I'm starting to appreciate what the buying time really means. It's hard with all that's going on but get your head straight and make sure you enjoy it.
Keep on keeping on.
> that was geared towards my specific mutation
This is actually one of the things that gives me hope for the future: genetic testing on a tissue sample of the patient's cancer is standard, and for many of the specific oncogenes that we know about, there exist therapies targeted to those specific mutations: https://www.cancer.org/cancer/lung-cancer/treating-non-small...
One thing I've learned is that even in the face of good news, cancer is a horrible time, and I wouldn't wish it on anyone. But I'm likewise glad to hear about your results from the latest treatment, and hope things stay as positive as they can for you.
I am hopeful we can move metastatic cancer (which is the true evil of cancer) to a controlled chronic condition.
BTW-- our oncology doctor believes in synergies between chemo and pembro, but I sometimes wonder if it's truly the chemo. Also, Pembro is not without its side-effects.
> I think they've been saying this for a long time now, but it's truer than ever that a real cure for cancer is right around the corner.
I think thats quite a leap. For prostate cancer( most common cancer among men), top line therapies are still androgen blockage that was discover 70 yrs ago, chemo and radiation. Keytruda failed to deliver any significant survival benefits[1].
Yes we've gotten better at slash, burn , poison methods. Radiation is more trageted and sophisticated. Diagnostics are more precise. Chemo drugs have better safety profiles.
But these are all marginal improvements. None of which indicate anything that we are close to a cure.
Only hope we still have is to catch it earlier and go ham on it. Most of the slash,burn, poison methods are being FDA approved for earlier use.
The other two things(one of which you've mentioned) are immune checkpoint blockade if you have MSI-hi/dMMR or PARP inhibition if you have BRCA2+. Even if you are lucky to have these mutations these drugs are a hit or miss[1].
I don't feel optimistic about a cure at all.
1. https://www.businesswire.com/news/home/20220803005334/en/Mer...
By "around the corner" I'm really talking about, like, 20-30 years out, which I think is fairly soon in terms of cancer treatment progress. You're right that it reads like a leap in the context of my comment.
The history of cancer (The Emperor of All Maladies is a good book covering the history) is full of promising adjuvants, drugs, protocols that fail to generalize well. There are a lot of reasons for this. With drugs, one is that Phase 3 clinical trials often have patients who are selected on the basis of them being likely to be among the best responders. But once the drug is approved and made available to all patients within a given indication – a fundamentally different population – an overwhelming positive response may be significantly more modest. In many cases, this has to do with a patient's tolerance of the side effects or the interaction of the drug with known or underlying comorbidities.
While I'm encouraged by the research in this article and could see the drug being part of a combination protocol, I'm hesitant that it will be "universal". And the mechanism, candidly, is downright scary – if I were running a Phase 3 for this (seems the trial cited was a Phase 2 demonstrating baseline safety in humans), I would want a very detailed articulation of how the technology ensures with a high margin of safety that the drug delivery is targeted to the tumor and no other tissues. The permeability of blood vessels in tumors would not be sufficient (and also does not seem "universal").
On a more personal note, I'm actually a computational biologist and have done quite a bit of work in cancer research (masters thesis, portion of my dissertation). My Mother was also diagnosed with a highly aggressive cancer of unknown primary (CUP) origin in her lung late last year (estimated stage IIIb for NSCLC, stage 4 for CUP/melanoma). Its location and heart involvement made it inoperable. Turned out is was a melanoma, which to be frank I quickly recognized down to the subtype upon reviewing the pathology reports. The lung oncologists were much more conservative; given the location, they weren't especially well-versed in melanoma, and presumed it was an adenocarcinoma with a rare presentation despite the staining for carcinomas being negative across the board. Luckily, we managed to convince them to split the difference on the standard of care – CarboTaxol (carboplatin + taxol) combination and immunotherapy (nivolumab and ipilimumab), all at once. The immunotherapy surely saved her life; unlike with carcinomas, chemo is roughly 5% effective (as in, any response whatsoever) for melanomas. About 70% of melanoma diagnoses respond to combination immunotherapy with about 15% going into full remission (memory is shaky on that last number, may be slightly higher). With >95 PDL-1 expression, she was one of the lucky ones – she had a full response on both imaging and pathological endpoints. That also made her tumor (or what was left of it) operable. She's two lobes and a chunk of heart lighter, but she's alive, healthy, and recovering well. And while I cringed when he did it, one of her oncologists dropped the "c word" after surgery in discussing her case. Knowing the foe, I'm much more cautious in contemplating whether any of this represents a cure. Psychologically, the uncertainty around the future maintains a heavy burden over her and our family. A 70% response rate sounds really good, but it's a very different calculus when you're living it.
But as you said, her path towards a cure wouldn't have been possible not too long ago – in her case, 10-15 years; ipilimumab was approved in 2011 and nivolumab in 2014. But 30% of people with melanoma are still non-responders to combination immunotherapy. And, while a handful of other (generally less effective) options exist, non-responses in melanoma are deadly, often within a year or two of diagnosis, and for most all cancers have an incredibly high opportunity cost.
I don't expect I'll be able to do much, but all of the treatments we've undertaken so far seem very dated (not able to resect, one round of radiation, temodar+avastin for the last year, just switched to CCNU+avastin). I'd love to know where the state of the art is at and know how to nudge/prompt his oncologists to be looking at it through that lens.
My email is in my profile, feel free to reach out privately.
The current approach of regular prostate exams + treatment isn’t perfect but it’s extremely effective.
Would love to find any references for this.
FDA has only approved BRCA+ and few others like PALB2 for genetic targeting. It doesn't really matter how many others mutations that are found they won't be targeted with PARP.
So the question becomes is PC less likely to have target-able mutations compared to others ?
> At a broad glance, prostate tumors have, on average, fewer mutations (0.7 per Mb) than other common cancers, such as breast (1.2 per Mb), bladder (7.1 per Mb), colorectal (3.1 per Mb), and melanoma (12.1 per Mb)
I can't find the original article in which I saw it stated that PC has a lower mutational burden but the above might be sufficient.
Brother's been a doctor about 15 years. Huge extended family is aging, and of course cancer creeps in. Of course family members call to get his opinion, and he's been wrong every single time(thankfully). Usually saying something like 'oh, she'll be dead within 2 years' and them living 6, or 8. And in one case calling something a death sentence that was actually, seemingly at least, cured.
It's entirely possible he's just a shit doctor, but I like to think it's that progress has moved a ton since he's studied up on it last.
A programmer who would ignore the developments since 2007 would be unusable.
On the other hand, there's a huge number of consultants for enterprises which still write .net 4 like it's 2008 and they're both happy and productive. Unless they're sent to a training, why bother learning new stuff?
Thanks for sharing anything you can. If more comfortable sharing in private, I can be reached at asuela1 at yahoo's email service (it's my spam account, but I'll check it if you tell me you wrote back there).
Surgery was not an option here because of the size and location of the mass, but after the initial course of chemo a PET-CT showed an 80% reduction in size. After some time on pembrolizumab, symptoms continue to improve and surgery may be back on the table soon.
(edited for a more accurate picture of maintenance treatment; thanks to borbulon for refreshing my memory)
And 80% reduction after that first course... Amazing. How long after the first course did they do the scan that showed that reduction?
Btw, very happy for you (and even moreso for your contact). Great news.
Since you're talking about immunotherapy not typically being a first-line treatment, I'll share a morbidly interesting fact that underscores some of the, er... quirks of the US medical system. The oncologist treating my relative initially staged my relative's cancer in the electronic health records as stage IV, despite no evidence of metastasis (the usual criterion)--he explained that he did this specifically in order to pursue first-line Keytruda (which is indicated for stage IV but not stage IIIC) and have it be covered by insurance.
https://oncologypro.esmo.org/meeting-resources/esmo-congress...
It is now standard of care for melanoma, for one, but it isn't successful for all cancers, (or even all melanoma mutations).
The most disturbing part is most people are unaware they are ill until relatively late stages of the disease.
If you live long enough, one will know many good people that go this way. It is a worthy area of research, as it improves the lives of many families. =)
Who knows how long it would have had time to mutate and grow otherwise. Early detection is a really important issue for cancer treatments.
Looks as promising as any other promising cancer therapy in phase I trials!
There is a renaissance in cancer drug delivery at present, exemplified by antibody drug conjugates. The tech in the article is very interesting, and a superb bioengineering effort. A caveat is that complex multi-unit therapies don’t have a great track record. They are hard to manufacture reliably, and have a very large optimisation volume, so it’s difficult to increment the development as you only have finite resources for human trials. Contrast this with small molecules where there is a well defined process over various chemical and pharmacokinetic factors, prior to testing in humans. We also lack a good system for developing and trialing ‘platform’ tech like this - the current system is set up for single drugs/combos to be tested and eventually reimbursed in each cancer type separately. If you have a platform for delivering tailored therapies agnostic of cancer type, you will run into many barriers. There is currently only one drug I know of simultaneously approved across multiple cancer types (pembrolizumab in mismatch repair deficient tumours, a rare population). So many challenges ahead of the hype here.
Stopping DNA replication across the body will be fatal. This is what eventually kills with radiation toxicity.
"Given that the EDV surface is coated with lipopolysaccharide (LPS), single-chain bispecific antibodies were attached to the EDV surface where one arm of the antibody is directed to the O-polysaccharide epitopes and the other arm is directed to a tumour cell surface receptor for example Epidermal growth factor receptor (EGFR) which is found on the surface of over 70% of solid tumours"
and
"The EDVs being 400 nm rapidly fall out of these fenestrations and enter into the tumour microenvironment and since they carry the bispecific antibody on the EDV surface, the anti-EGFR component binds to EGFR on the tumour cell surface. This provokes macropinocytosis and the EDVs are taken into the early endosomes, followed by lysosomes and broken down in these organelles releasing the drug PNU-159682. The drug enters into the tumour cell cytoplasm and the nucleus and intercalates with the chromosomal DNA resulting in tumour cell apoptosis. In the event that a tumour type does not express EGFR for example liver cancer, which expresses asialoglycoprotein, then the bispecific antibody can be changed to anti-asialoglycoprotein while the anti-O-polysaccharide component remains constant. Similarly, HER-2 positive breast cancers can be targeted via anti-HER2/anti-O-polysaccharide bispecific antibody"
https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.111...
I don't think this particular therapeutic automatically homes to all cancer cells. However, certain bacteria have been found to home to cancer cells, so maybe that helps too. https://wis-wander.weizmann.ac.il/life-sciences/cells-inside...
It is very exciting to see another tool in the toolbox to achieve higher cancer cell therapeutic specificity.
Brahmbhatt and his collaborator Jennifer MacDiarmid devised a clever ploy. They would send a Trojan horse into malignant cells and turn cancer’s own trickery against it.
The Trojan horse, in this case, is a product of a harmless bacteria that’s been genetically engineered to have specific qualities. When this genetically engineered bacteria divides, it yields a tiny non-living cell of 400 nanometers in diameter—the right size to slip through the damaged vessels and mingle with the tumors."
Targeting the cancer's vascular supply is also a known anti-cancer mechanism of action (anti-angiogenics). How will this method not have the same toxicity as that one?
1. The Somatic theory of cancer ('bad genes/out-of-control cellular replication')
2. The metabolic theory of cancer ('cancer cells ferment blood sugar for energy via an ancient emergency metabolic pathway')
Both have merit, but a complete occlusion of one would be bad.
I wrote an open letter, long ago, to a wealthy person who was on the board of a cancer research center, suggesting they read a book and fund the key research scientist:
https://josh.works/mike-clayville-can-have-a-huge-impact-on-...
I thought of the metabolic theory of cancer as I opened this page, because all cancers have a similar reliance upon certain energy generation pathways, which implies a corresponding vulnerability for treatment.
Some people find it interesting enough to click through, read the article, and to read the book.
oh boy
Eg https://www.cancer.gov/research/key-initiatives/ras/ras-cent...
Obviously not usually considered cause, but rather effect.
Tl:dr: Things usually work in the lab where all ideas start. Until a compound goes through thorough human experimentation believe little.
The issue is large companies (novartis/BMS) sometimes sit on compounds and refuse to develop because they think it may not be worth it, may think a certain disease (read market) is saturated, or they may be waiting for the 'right time'. It can be frustrating.
Smaller companies have 2-3 compounds which they actively work to develop but most of them end up getting acquired by the big fish.
As long as the cancer isn't in the patient's brain, the patient's head could be removed and transplanted onto a donor (brain dead) body. This would render the patient a quadriplegic, but with repeated study over decades we might be able to repair the nervous system.
There isn't a large set of brain dead bodies to draw from, so if this process proves successful, perhaps we could one day start growing human bodies in labs from a monoclonal source. If we remove their ABO and MHC antigens, we might be able to lessen the need for an ongoing life-altering immunosuppressant regimen. These lab grown bodies would be headless/brainless from the outset via gene and surgical deactivation during development to remove any ethical issues. The bodies could be artificially innervated and pumped with the hormonal signals they need to grow until it's time to harvest them.
Cancer is thousands and thousands of different disease states, and it will remain a difficult landscape for the foreseeable future. A non-molecular approach of wholesale cancer tissue removal (via body replacement) seems like an out of the box solution that could work.
What happens once they stop the growth of cancer, say in the case of a tumour? Will it break down over time or does it need to be surgically removed?
The researchers main concern was whether those nanoncells would also enter healthy cells, but the tests seem to show healthy cells were not affected.
Quick question: Based on this statements would these therapy work particularly well against metastatic disease given its moa for cell selectivity?
Whats the best way to detect cancer (money is no object) and how do we get that cost down 10x and get everyone to participate?
To be clear, I very much think that early detection of tumors will someday be an essential part of cancer treatment. We are not there yet.
This isn't necessarily the case. A lot of CTCs have markers that are indicative of certain cancers or tissue types of origin. Different tissues have specific patterns of gene expression even if they all have the same underlying DNA, and there are databases with thousands of samples sequenced supporting these patterns.
I understand the cost, time, etc. but I still think if we can stop doing other useless stuff as humanity and do this it would be net positive.
Very interesting comment, nonetheless.
- False-positive results
- False-negative results
"Mammograms are the best breast cancer screening tests we have at this time. But mammograms have their limits. For example, they aren’t 100% accurate in showing if a woman has breast cancer. They can miss some cancers, and sometimes they find things that turn out not to be cancer (but that still need further testing to be sure)."
https://www.cancer.org/cancer/breast-cancer/screening-tests-...
https://www.dartmouth-hitchcock.org/stories/article/norris-c...
https://www.bloomberg.com/press-releases/2022-02-02/newly-pu...
https://www.prnewswire.com/news-releases/engeneic-announces-...
It's a scam.
> so this can put the breaks on cancer, but it can't fix cancer?
"Putting the brakes on cancer" is basically equivalent to "fixing cancer". For my Dad's GBM, he has an MRI from 13 years before his diagnosis that seems to show the early stages of his tumor. At the time, his neuro noted that it was mildly concerning, but then didn't order any follow-up testing. So the tumor lay "dormant" in my Dad's head for over a decade. Then it started rapidly growing last year, until he was losing his balance at work, started getting scans, and eventually found the brain tumor.
All of the standard of care around this is focused on mechanical or electromagnetic removal of large parts of the tumor, combined with throwing whatever chemotherapies you can at the body to stop the tumor from growing. Eventually, the tumor grows until it squeezes out all normal brain functionality. Anything that can arrest the tumor without killing you is good.
I mean untargeted chemotherapy kills -the one thing- that protects us since before we were born from cancer, our immune system.
Killing our immune system to kill cancer makes as much sense as shooting off the leg you lead with so to run faster.
Its idiotic, stupid and, yeah its basically trying to stop the copy errors in genes that cancer does, before all the massive amount of DNA errors kill the cancer victim ...
It's like a really really bad CRISPR process as I understand it, like the computer program SED was majorly crapping out and it made your program an utter mess.
Anyway, chemotherapy is DAMN foolish, and I for one will be glad when we're rid of it with better therapies
There's a lot of money in suffering, and if you think there aren't people sick enough out there to do real horrible shit to protect that income stream, you're kidding yourself.
How do you think this fucked up civilization was twisted into the giant pulsating tumor it currently is?