[HN Gopher] A Universal Cancer Treatment?
___________________________________________________________________
A Universal Cancer Treatment?
Author : WithinReason
Score : 216 points
Date : 2022-10-06 15:38 UTC (7 hours ago)
(HTM) web link (nautil.us)
(TXT) w3m dump (nautil.us)
| wonder_er wrote:
| I can't help but mention that there are two dominant schools of
| thought regarding cancer treatments:
|
| 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.
| Animats wrote:
| Has this been written up in some respected journal? (No, not
| Nature.)
| jjtheblunt wrote:
| Their research was published in Cancer Cell.
|
| https://www.prnewswire.com/news-releases/engeneic-announces-...
|
| https://engeneic.com/
| qclibre22 wrote:
| Othes by Stillman :
| https://scholar.google.com/citations?user=ANthHuAAAAAJ&hl=en...
| lwansbrough wrote:
| Did I miss it or was the delivery mechanism not really mentioned?
| I suppose that might be the secret sauce?
|
| 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?
| axus wrote:
| I think it was modified yeast bacteria produce a cell of
| exactly the right size to slip through the same blood vessels
| that the cancer did when it spread; unaffected blood vessels
| wouldn't let anything through.
| bottombutton wrote:
| They genetically engineered a kind of bacteria that divides
| into non-living 'nanocells' that can't multiply further. These
| cells contain a special kind of RNA and a cell entry mechanism
| that lets them enter the cancer cells. The RNA interrupts the
| cell's ability to prepare for division. The article kind of
| implied that these nanocells follow the bloodstream pathways
| that cancer cells open when they metastasize.
|
| The researchers main concern was whether those nanoncells would
| also enter healthy cells, but the tests seem to show healthy
| cells were not affected.
| nikivi wrote:
| I loved Michael Levin's thoughts on solving cancer. Kind of
| similar to immunotherapy but on a level of reprogramming the
| cells back that got 'lost' from their big purpose in their organ.
|
| https://www.youtube.com/watch?v=p3lsYlod5OU&t=8653s
| ncmncm wrote:
| Michael Levin is an astonishing breath of fresh air.
| echelon wrote:
| 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.
| breck wrote:
| https://engeneic.com/intellectual-property/
|
| It's a scam.
| xchip wrote:
| Paper from a peer reviewed repo, not press releases please
| sam537 wrote:
| Oncologist here. You can think of drug development as an
| extremely wide funnel with a minuscule exit hole. At any given
| time a medium sized pharmaceutical company has 300-500 drug
| candidates. From this group 50 make it to phase 1 trials. 40 get
| slashed due to toxicity, company abandons them, gets bought by
| third party and sits in sleepy storage. 10 advance to phase 2
| trials where 5-8 may not end up having enough efficacy/too toxic,
| does not improve survival. The remaining 3-5 advance to phase 3
| where they can suffer the above as well.
|
| Tl:dr: Things usually work in the lab where all ideas start.
| Until a compound goes through thorough human experimentation
| believe little.
| dvirsky wrote:
| Sounds like this one is pretty advanced down the funnel, having
| successfully passed phase 1 human trials, or am I missing
| something?
| abcc8 wrote:
| 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.
| tempestn wrote:
| 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.
| nighthawk454 wrote:
| Thanks, that's an interesting insight into the dropoff rate for
| these ideas. Do you have an opinion on what the bottleneck is?
| Volume of ideas, length of testing, or perhaps flawed approach
| in general?
| pfdietz wrote:
| The extreme complexity of biology. There's no substitute to
| just trying things and seeing if they work, because you will
| never understand what's going on beforehand.
| dominotw wrote:
| funny how many of blockebuster drugs were discovered by
| accident.
| pfdietz wrote:
| And for some that were designed to hit a specific target,
| it was discovered afterwards that they work by a
| completely different mechanism.
| sam537 wrote:
| This is the bottleneck for one company. We have many
| companies this size doing the same thing.
|
| 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.
| ncmncm wrote:
| Thanks. I had read of success infecting tumors with virus, that
| the immune system will control only outside the tumor. But I
| didn't hear any more about it. What happened with that?
| breck wrote:
| I ctrl+f for "patent" and got no hits, so forwarded it to someone
| on our team to dive in to further.
| NetWonk_me wrote:
| 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 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
| slyrus wrote:
| I'd argue that our future retrospective view of chemotherapy
| will be more of how we view hunting with a club rather than,
| say, a bow and arrow. Not optimal but, at least in many cases,
| proven to be better than nothing by multiple randomized
| clinical trials.
| sonofaragorn wrote:
| If you got cancer and the onclogist recommended chemo, would
| you refuse it?
| [deleted]
| yshrestha wrote:
| 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.
| asdff wrote:
| It does, from the article: ""Normally, our blood vessel walls
| are all sealed pipes," Brahmbhatt says. "But around wherever
| the cancer is growing, the blood vessels are known to be very
| defective. They have got a lot of holes in them."
|
| 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."
| yshrestha wrote:
| I see. I do wonder how specific that is though. Potentially
| it could be toxic to other areas where vasculature could be
| "leaky". Like in the filtration mechanisms in the kidney.
|
| 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?
| asdff wrote:
| Presumably that 400nm size is important for specificity as
| well
| pazimzadeh wrote:
| 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...
| JanSt wrote:
| Does anyone know about updates on mRNA treatments for cancer? I
| had big hopes after the impressive corona-virus vaccines. I know
| BioNTech is investing heavily but not much has changed since
| then?
| sam537 wrote:
| There are a few vaccines that try to 'make' your immune system
| recognize an abnormal (read cancerous) protein as foreign
| (Sipleucel T for prostate, GMCSF vaccine for melanoma). Minimal
| activity.
| Lytic42 wrote:
| 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?
| Joel_Mckay wrote:
| 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 way. It is a worthy area of research, as it improves the
| lives of many families. =)
| heavyset_go wrote:
| 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.
| dominotw wrote:
| liquid biopsy seems promising in early detection.
| JanSt wrote:
| Yes, my cancer was discovered pretty early by pure chance in a
| CT for an unrelated issue. I had zero symptoms, was really fit
| and pretty much never sick.
|
| Who knows how long it would have had time to mutate and grow
| otherwise. Early detection is a really important issue for
| cancer treatments.
| Kalanos wrote:
| so this can put the breaks on cancer, but it can't fix cancer?
| notdonspaulding wrote:
| 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.
| bulbosaur123 wrote:
| When could we realistically see this solution for someone with
| prostate cancer?
| mentos wrote:
| Early detection?
|
| 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?
| chrisamiller wrote:
| Money is absolutely an object. People are starting to do trials
| of early detection from circulating tumor DNA, and finding that
| the hit rate is alarmingly high. A decent portion of the
| population has some kind of malignancy, but most of these will
| either be cleared by the immune system, or be completely
| benign. Another problem is, if we detect this tumor DNA, it
| doesn't tell us where in the body the tumor might be. So then
| you're talking massive workups including while body CT scans
| and such for a problem that isn't going to be a problem for 99%
| of people. I'm not joking when I say that if rolled out as is,
| this has the potential to bankrupt the entire healthcare system
| with unnecessary procedures.
|
| 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.
| asdff wrote:
| >Another problem is, if we detect this tumor DNA, it doesn't
| tell us where in the body the tumor might be.
|
| 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.
| Nathanael_M wrote:
| I think the question being asked was "If money were no
| object, what is the best cancer detection method?", as
| opposed to stating that money wasn't an object.
|
| Very interesting comment, nonetheless.
| sam537 wrote:
| Look at GRAIL therapeutics. Cancer sheds DNA that can be
| detected and amplified. We use this sometimes to try to tell if
| someone will have a recurrence before scans actually show it.
| Sequencing is hard, and there are contaminants and difficulties
| calling a mutation/sequence cancerous, but I have had patients
| self-refer after a positive GRAIL test, no symptoms, and bam,
| biopsy from area of interest shows early cancer.
| pella wrote:
| problems:
|
| - 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-...
| selectodude wrote:
| Furthermore the detection method used (x-rays) cause cancer
| in and of themselves.
| Buttons840 wrote:
| https://xkcd.com/radiation/ lead me to believe that most
| x-rays only expose the person to a few days worth of
| background radiation. Is that accurate? And does it really
| matter?
| asdff wrote:
| You can detect tumor cells circulating in blood for certain
| cancers. You can get the cost down by having these tests
| covered at regular intervals by insurance companies.
| throwaway12245 wrote:
| Or make it over the counter and pay the $500.
| nyx wrote:
| It really is remarkable how far cancer treatment has progressed,
| even in the last few years. I'm one of the unfortunate people
| who, through a close family encounter with cancer, knows more
| about this stuff than anyone should have to. The oncologist told
| my relative that if they had presented with this particular
| cancer just a decade ago, his recommendation would have been to
| start hospice care.
|
| 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.
| bongoman37 wrote:
| This. A close friend of mine was diagnosed with stage III
| stomach cancer. He lost massive amounts of weight and I almost
| thought he was not going to make it. And a year later he is
| back at work and doing pretty well.
| dominotw wrote:
| > 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
| 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...
| 01100011 wrote:
| Prostate cancer is, from what I understand, one of the
| cancers with the least amount of genetic differences from
| normal tissue. That makes it harder to target. It also
| explains the general failure of checkpoint inhibitors.
| nyx wrote:
| 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
| treatment progress. You're right that it reads like a leap in
| the context of my comment.
| bnjemian wrote:
| 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.
| notdonspaulding wrote:
| My Dad is currently battling a GBM. Do you have any
| advice for a web dev who wants to get his toe in the door
| of understanding the computational biology of gliomas?
|
| 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.
| Retric wrote:
| Part of this is because prostate cancer has such a high
| success rate. With treatment, the 5 year survival rate for
| early prostate cancer is over 99%, and is was close to 98% 20
| years ago.
|
| The current approach of regular prostate exams + treatment
| isn't perfect but it's extremely effective.
| asdff wrote:
| As others have mentioned it depends. For instance the initial
| trials with pembrolizumab weren't the silver bullet the media
| makes them out to be today, until they identified what features
| might common among patients that did see a response, e.g.
| mismatch repair deficient cancers, because the tumor needs to
| be spitting out enough of these tumor-specific neoantigens to
| be targted by the immune system. That generally happens with
| highly mutated tumors such as those found in mismatch repair
| deficient tumors. The reason why the immune system was not
| targeting the tumors like it should have given the neoantigens
| until you take the drug is because the tumor cells presents the
| correct receptors that the immune system expects from healthy
| cells, which prevents the immune response. When you block that
| receptor as these drugs do, and also have many of these tumor
| specific neoantigens being expressed, then the immune system is
| able to target the tumor cells for death and the drug works
| well.
| borbulon wrote:
| As a person who currently has stage IV NSCLC, I can add some
| context to this:
|
| 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.
| nyx wrote:
| Thanks for sharing your story and treatment details. I should
| add that my relative's cancer has no particularly interesting
| mutations, but does have a high PD-L1 expression, which from
| what I can tell is the reason Keytruda was more likely to
| work for their situation.
|
| > 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.
| ghjnut wrote:
| I was diagnosed with stage III NSCLC February '21. Radiation,
| chemo, and a bilobectomy. I had the ALK+ morphology which
| meant I wasn't a candidate for immunotherapy but I've been on
| alectinib since my surgery in June '21 with no signs of
| recurrence so far.
|
| 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.
| tomcam wrote:
| Shit. My best to you and yours. Thanks for sharing.
| harmmonica wrote:
| Would you be willing to share the type of cancer? Also, was the
| person you're referring to (can't tell if it was a relative)
| able to bypass traditional chemotherapy and go straight to the
| immunotherapy given the prognosis? Or did the oncologists
| require chemo first and only then your contact was able to
| receive the immunotherapy?
|
| 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).
| nyx wrote:
| Stage IIIC NSCLC, specifically a superior sulcus tumor,
| advanced enough to be considered inoperable. Standard of care
| in this case was induction radiotherapy, followed by a single
| course of combination chemotherapy consisting of carboplatin,
| pemetrexed, and pembrolizumab (the last of which is the
| cutting-edge immunotherapy I'm talking about; brand name
| Keytruda.) After that, patients are prescribed the pemetrexed
| and immunotherapy alone for a long 2-year "maintenance"
| course, at which point treatment options will be reassessed.
|
| 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)
| harmmonica wrote:
| Thank you for pointing out the standard of care in this
| case, given inability to resect, was the immunotherapy from
| the start. Obviously very specific for that type of lung
| cancer and the state of your contact's tumor, but I've been
| learning more and more about this and have been told by
| multiple oncologists that immunotherapy is typically only
| given after more conventional treatments are first
| attempted and fail to stop progression or shrink the
| mass(es). Needless to say that's far from categorical so in
| my next conversations I can be a bit more educated in my
| questioning.
|
| 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.
| nyx wrote:
| 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 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.
| PuppyTailWags wrote:
| 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.
| xyzzyz wrote:
| 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.
| harmmonica wrote:
| Thanks for the info on the timing. And that's my kind of
| oncologist. Risk in doing that on multiple levels, of
| course, but reassuring that some physicians are willing
| to do what's right vs what fits into into an insurance
| company's flow chart.
| mcbain wrote:
| Of course it varies by cancer. Look up "adjuvant
| immunotherapy".
|
| It is now standard of care for melanoma, for one, but it
| isn't successful for all cancers, (or even all melanoma
| mutations).
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