Live data from Hacker News

A Universal Cancer Treatment?

nautil.us

61–70 of 100 posts

Re: A Universal Cancer Treatment?

#61
post #7

so this can put the breaks on cancer, but it can't fix cancer?

I'm far from an expert, but my Dad is currently battling a high-grade glioblastoma multiforme tumor in his brain. So I've learned a little.

> 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.

Re: A Universal Cancer Treatment?

#62

Someday soon they'll look at our insane chemotherapy with the same level of utter disbelief as we do about bloodletting and tapeworm diets 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 ba…

If you got cancer and the onclogist recommended chemo, would you refuse it?

Re: A Universal Cancer Treatment?

#63

I may be missing something but the article does not explain how the bacteria target is actually targeting the cancer cells. Of course, if you can design an ideal universal cancer targeting mechanism, the active ingredient itself is beside the point. Did anyone else catch this? Stopping DNA replication across the body will be fatal. This is what eventually kills with radiation toxicity.

The article is missing lots of detail. They use antibodies to target receptors which are highly expressed by tumors, such as Epidermal growth factor receptor (EGFR).

"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...

Re: A Universal Cancer Treatment?

#65
post #46

Earlier quoted context omitted.

The scan that indicated the 80% reduction was after just a couple of weeks, if I recall correctly. 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…

I don't understand how medical insurance companies can choose what treatments can be applicable to what patients and yet not be as liable as a doctor for medical malpractice.

It’s not that they choose the treatment, you can get whatever treatment you want. They just say that they won’t pay for treatment other than X. This is unavoidable, really: if you look at countries with public healthcare system, like eg. UK, the (state) insurer there also makes decisions as to which treatments are covered, and which patients are eligible to get them. If anything, they are more conservative than private insurers in US: due to public nature, typically they do not offer higher range of treatments to customers who pay higher premiums. Instead, the coverage is “one size fits all”, and to limit costs, covered treatments options are seriously limited compared to what private insurers offer in US, especially in countries other than the wealthiest ones: in Poland, for example, cancer treatments available to patients on government healthcare are at least a decade or two behind the state of the art. Of course, the flip side is that you then get to see how cheap health care per capita is in Poland, and gripe about outrageous costs in US.

Re: A Universal Cancer Treatment?

#66
post #12

Earlier quoted context omitted.

> in recent years, a very effective checkpoint inhibitor immunotherapy has been developed for the cancer in question. ~2x the success rates of traditional chemo > 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 bloc…

I agree that my original comment is very optimistic--for what it's worth, Keytruda has thus far been very effective in the case I'm talking about, so I have some bias here. I concede that even in my "double the effectiveness" example, we're talking about doubling something like a 20% 5-year OS. By "around the corner" I'm really talking about, like, 20-30 years out, which I think is fairly soon in terms of cancer trea…

Not to be too pessimistic, but 600,000 people died of cancer in 2019, so 20-30 years is hardly "round the corner" when you extrapolate to the, let's say conservatively, 10 million families in the US losing loved ones in that time period.

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.

Re: A Universal Cancer Treatment?

#67

It is not a single disease, but rather a result of several errant biological outcomes. The mortality rates have improved a lot with better treatments, and around 60% of the population will develop some form of the disease in their lifespan. 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…

Screenings allowed my family members to catch cancer early when they still had chances for good prognoses, so don't skip out on regular checkups.

Re: A Universal Cancer Treatment?

#68
Some quick thoughts. This therapy uses a combination of methods that are already used in oncology. The usage of bacteria in oncology as part of immunotherapies has existed for decades via the use of BCG, although it is notably that these bacteria have genetic modifications to allow it to create a delivery vehicle as well. siRNAs have always been an attractive method but lacked proper delivery methods and initially had issues with degradation. The knockdown of DNA polymerases is new to me. Typically chemotherapeutics are anti-metabolites or seek to arrest mitosis (taxanes for example lock part of the cytoskeleton [microtubules] needed to move chromosomes). Targeting DNA polymerase makes fundamentally more sense because you would by and large avoid disrupting other cellular functions. Hopefully this represents another tool in the kit in regards to conjugate/combination therapies like Trastuzumab-deruxtecan.

Quick question: Based on this statements would these therapy work particularly well against metastatic disease given its moa for cell selectivity?

Re: A Universal Cancer Treatment?

#69
The universal cancer treatment will be full body transplant.

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.

Re: A Universal Cancer Treatment?

#70
post #47
post #42

Earlier quoted context omitted.

Sounds like this one is pretty advanced down the funnel, having successfully passed phase 1 human trials, or am I missing something?

Phase 1 trials are used to determine drug toxicity. All that reault really says is that the new drug won't itself kill the patients. It still needs to be compared relative to the standard of care in larger phase 2 and 3 trials.

However, the article also describes patients in the trial having positive effects. Yes, it's not an efficacy trial, but if it was specifically used on patients who have exhausted all other clinical options, there were no significant adverse side-effects, and there were beneficial effects for some substantial number of patients, that sounds pretty hopeful to me. Of course it's possible issues will still be discovered, but this is a long way from a top-of-funnel lab result.
Post reply on HN