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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

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August 16, 2010

Cancer Cells: Too Unstable For Fine Targeting?

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Posted by Derek

The topic of new drugs for cancer has come up repeatedly around here - and naturally enough, considering how big a focus it is for the industry. Most forms of cancer are the very definition of "unmet medical need", and the field has plenty of possible drug targets to address.

But we've been addressing many of them in recent years, with incremental (but only rarely dramatic) progress. It's quite possible that this is what we're going to see - small improvements that gradually add up, with no big leaps. If the alternative is no improvement at all, I'll gladly take that. But some other therapeutic areas have perhaps made us expect more. Infectious disease, for example: the early antibiotics looked like magic, as patients that everyone fully expected to die started asking when dinner was and when they could go home. That's what everyone wants to see, in every disease, and having seen it (even fleetingly), we all want to have it happen again.

And it has happened for a few tumor types, most notably childhood leukemia. But we definitely need to add more to the list, and it's been a frustrating business. Believe me, it's not like we in the business aiming for incremental improvements, a few weeks or months here and there. Every time we go after a new target in oncology, we hope that this one is going to be - for some sort of cancer - the thing that completely knocks it down.

We may be thinking about this the wrong way, though. For many years now, there have been people looking at genetic instability in tumor cells. (See this post from 2002 - yes, this blog has been around that long!) If this is a major component of the cancerous phenotype, it means that we could well have trouble with a target-by-target approach. (See this post by Robert Langreth at Forbes for a more recent take). And here's a PubMed search - as you can see, there's a lot of literature in this field, and a fair amount of controversy, too.

That would, in fact, mean that cancer shares something with infectious disease, and not, unfortunately, the era of the 1940s when the bacteria hadn't figured out what we could do to them yet. No, what it might mean is that many tumors might be made of such heterogeneous, constantly mutating cells that no one targeted approach will have a good chance of knocking them down sufficiently. Since that's exactly what we see, this is a hypothesis worth taking seriously.

There are other implications for drug discovery. Anyone who's worked in oncology knows that the animal tumor models we tend to use - xenografts of human cell lines - are not particularly predictive of success. "Necessary but nowhere near sufficient" is about as far as I'd be willing to go. Could that be because these cells, however vigorously they grow, have lost (or never had) that rogue instability that makes the wild-type tumors so hard to fight? I haven't seen a study of genetic instability in these tumor lines, but it would be worth checking.

What we might need, then, are better animal models to start with - here's a review on some efforts to find them. From a drug discovery perspective, we might want to spend more time on oncology targets that work outside the cancer cells themselves. And clinically, we might want to spend more time studying combinations of agents right from the start, and less on single-drug-versus-standard-of-care studies. The disadvantage there is that it can be hard to know where to start - but we need to weigh that against the chances of a single agent actually working

Comments (49) + TrackBacks (0) | Category: Animal Testing | Cancer | Clinical Trials | Drug Development


COMMENTS

1. FMC on August 16, 2010 9:45 AM writes...

In light of the previous threads, I would thoroughly recommend to outsource that kind of problem to some outfit in India or China, while at the same time taking credit for this new and visionary approach to increase ROI !!!
:)

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2. alig on August 16, 2010 9:51 AM writes...

I thought it was going to be less depressing topics this week.

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3. BiotechMan on August 16, 2010 10:04 AM writes...

The industry over the past 10 years or so has been progressively more risk-averse. This is in part due to Wall Street not rewarding innovation and this is reflected in the venture world where "repurposing" was the name of the game. Newer approaches to attacking cancer taken by folks at Agios and Ruga targeting tumour metabolism, endoplasmic reticulum stress etc. may be the wave of the future.

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4. A Nonny Mouse on August 16, 2010 10:21 AM writes...

I thought that the new approach was cancer stem cells.

An "add-on" clinical trial (for CML) is currently on-going in Mass using a marketed drug which does just that.

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5. barry on August 16, 2010 10:45 AM writes...

We still don't know how many diseases cancer is. In the extreme, it might be a swarm of many diseases most of which are too rare to warrant drug development. I don't believe that, but we're not doing well here.
Because the genomes of cancer cells are unstable, it is very hard to succeed at killing an old established cancer--it's more likely to end-run anything we blockade. Alas, these are precisely the cases we choose for clinical studies. It is likely that drugs which would have succeeded against some early cancers (which had fewer mutations) have already failed in the clinic because of the clinical population chosen.

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6. metaphysician on August 16, 2010 11:15 AM writes...

[layman]

Honestly, is it even really clear that 'cancer' is a disease, as opposed to a symptom/failure mode?

[/layman]

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7. 杀獁特の鳮芼 on August 16, 2010 2:28 PM writes...

@A Nonny Mouse
I'm still not totally sold on the cancer stem cell theory, and I believe there is still quite a controversy on this topic today, which is nearly 15 years after Dick's first paper on CSC. Particularly, it doesn't make a lot of sense to me that a tumor would waste so much resource to make tons of differentiated tumor cells, if only the tumor initiating cells are the ones doing the harm. Conventional adult stem cell theory states that stem cell is responsible for proliferation and differentiated cells are responsible for interaction with surrounding enviornment in a mature organ and act as functional units.

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8. Anonymous on August 16, 2010 2:30 PM writes...

Nahhhh. There's all kinds of nihilism expressed by frustrated scientists attempting to develop effective anticancer drugs. All the excuses can basically be summarized as "Its not me, its the XXXX characteristic of the cancer cell."

Wrong. Its just very very hard to develop anticancer drugs since cancer cells (unlike, for example bacteria and viruses) are very very similar in almost all respects to normal human cells. Can you think of a single disease that has been cured (other than some forms of cancer) in which the pathogenic cell that needs to be eliminated is human? Me neither.

Cancer is really really hard. No more excuses. Get back to the lab.

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9. Anonymous on August 16, 2010 2:35 PM writes...

BTW, re: the cancer stem cell thing. This is a great example of a situation where the smartest cancer scientists are basically keeping their mouths shut and waiting for the fad to go away. Very few serious cancer biologists believe much of the cancer stem cell hypothesis, and basically no cancer geneticists believe it. There is just no upside re: saying it in public. Just like the incredible focus on apoptosis in cancer 10-15 years ago, the smartest cancer scientists are just waiting for it to peter out while they keep plugging away at the unsexy fundamentals....

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10. barry on August 16, 2010 2:36 PM writes...

any vaccine that elicits a T-cell response eventually works against disease by destroying a host cell. Perhaps that doesn't qualify as "drug".

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11. LAM on August 16, 2010 2:45 PM writes...

It is highly unlikely that a single "new" approach will "cure" cancers in our lifetimes. Success will continue to be defined by incremental or stepwise improvement in treatments toward endpoints that are meaningful. Whatever the "newest and best" approach, be it selective kinase inhibition, protease intervention, manipulation of stem cell function, T-cell stimulation, no single one is likely to be "the magic bullet", the "key in the lock" for bringing the cancer epidemic under control.

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12. Gillespie on August 16, 2010 4:31 PM writes...

What about tageting glycolysis? Maybe Otto Warburg was onto something. No matter how the cancer cells change genetically, they still have to make ATP, and for many reasons, Ox-Phos doesn't cut it for them, while it works in normal cells.

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13. Andy Pierce on August 16, 2010 5:40 PM writes...

There are a few companies (like Agios) taking a look at the Warburg effect.

The genomic instability of cancer cells has been exploited chemotherapeutically already. For example, many cancer cells are checkpoint defective but this means that normal cells when treated with genotoxic agents halt the cell cycle and repair the damage while cancer cells just blithely divide on into catastrophe. Much more could be done in this area.

Personally, I blame mice for the lack of progress in cancer therapeutics. People (especially academics) have been so busy curing cancer in mice that they haven't figured out how to cure cancer in people. The only good animal model for human cancer is humans, so that's where the experimental drugs should go. I think in part lack of a "good animal model" is what has helped propel HIV treatment to where the disease has gone from death-sentence to mostly chronically manageable.

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14. Anonymous on August 16, 2010 8:01 PM writes...

There are a handful of cancer-like conditions that have benefited from cancer research. (The potential use of Gleevec for treatment of NF comes to mind.)

Of course, providing therapies for these rarer diseases may not be as important as taking on cancer, but let's not forget about them.

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15. barry on August 16, 2010 8:35 PM writes...

While mice dominate cancer research, they're not all alone. For a price, one can treat surgically isolated human cancers grown in nude rats, rather than cancer cell lines that have been selected for growing in culture. There are also spontaneous cancers in old pet dogs, but never enough of them to get statistical answers out.

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16. Charlie Abrams on August 16, 2010 9:49 PM writes...

I think epigenetic drugs (eg. Vorinostat) might have some promise. I remember something from a Breslow talk in Chicago: he said the most active in-vitro compound was too toxic, and the breakthrough was in part the result of looking at the less-potent compounds. Also, the treatment is like hitting the reset button - you don't just keep pounding, you treat for a week or two and then stop. Are these two strategies (less potent/short treatment) part of the usual pipeline development methods?

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17. David Young MD on August 16, 2010 11:56 PM writes...

If scientists can get linkers to work correctly, antibody-cytotoxin complexes may be a major advance. Where-as mylotarg was a failure, some second generation compounds may end up working very well. We'll see.

All the same, the continuous mutability of cancer cells is a major obstacle to a cure... no doubt about it.

Permalink to Comment

18. Phd Biochem on August 17, 2010 9:19 AM writes...

I did a cancer-related postdoctoral fellowship several years ago, on signal transduction. I realized then that cancer was not going to be stopped by signal blockers or anti-angiogenesis drugs. In my opinion, the most likely chance for success is using the immune system to target the cancer. As the cancer evolves, antibodies of different specificities will be needed. The end state would be vaccines against the most common cancers, and immunotherapy for the more rare forms. Chemotherapy-linked antibodies would be a variation on the theme. We must leverage the body's own sophisticated defense system, and teach it to recognize attacks that natural selection has not caught up to yet.

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19. Douglas Cohen on August 17, 2010 9:43 AM writes...

Biological systems strengthen themselves under the influence of moderate stress (think exercise to promote better circulation and stronger muscles) and weaken when underused. With modern medical science (antibiotics) and the relative scarcity of serious bacterial infections -- defined as causing a fever -- in today's developed countries, the branch of the immune system designed to handle single-cell pathogens has, in most people, become a serious couch potato. If this is the branch of the immune system evolution has designed to recognize and suppress cancer cells, we would expect more and more people in developed countries to die of cancer at every age -- including old age -- than do in undeveloped countries due the developed countries' couch-potato immune systems. To get these immune systems into shape, develop pathogenic bacteria bred to be strongly susceptible to your antibiotic of choice, and infect people at regular intervals with this bacteria, arranging for their immune system to generate a meaningful fever before quelling the infection. If it looks like the infection is gaining the upper hand, administer the antibiotic and after recovery try to tone up the patient's immune system with a weaker source of infection. You may even get lucky, and find that cancer patient's can be cured by toning up their immune system with a tailored course of infections (if the disease has not yet progressed too far and the immune system has not been significantly damaged by current treatments for cancer). There is evidence in the medical literature of good results for cancer patients purposely infected by doctors to produce high fevers (in the early years of the twentieth century). Back then doctors suspected that fever was the curative factor, but from the point of view of the couch-potato hypothesis it was the infection itself, building up the immune system (This line of research, by the way, fell out of favor with the discovery that X-rays shrank tumors. Now, of course, we know all too well the limitations of X-ray therapy)

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20. noahp on August 17, 2010 10:25 AM writes...

Retired from Radiation Oncology 7 years ago in part because of frustration with the "standard of care" enforced by the Medical Oncology mafia. Many patients apparently including Christopher Hitchens are treated with toxic cheotherapy regimes without the slightest evidence of efficacy. I practiced in Memphis for eleven years and cured the only patients with esophageal cancer that were cured in that city. Esophageal cancer is a fairly rare disease...the patients with insurance are scooped up by the surgeons and medical oncologists and they all die. The dregs of society were the ones I treated with about a 40% cure rate among those without apparent distant metastases. But I was never able to convince my "colleagues" that my results were anything other than anecdotal.

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21. Chuck Pelto on August 17, 2010 11:11 AM writes...

TO: Derek Lowe, et al.
RE: Cancer Cures

You REALLY need to look into graviola and pawpaw.

I've SEEN pawpaw kill an aggressive squamous carcinoma on a woman's arm in just ONE MONTH. And, based on my understanding of the mechanism, it should be effective against most forms of cancer.

Regards,

Chuck(le)
[God made the Earth and everything therein for Man. Our problem has been trying to figure out how to use it....properly....]

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22. Chuck Pelto on August 17, 2010 11:19 AM writes...

P.S. That graviola was capable of killing cancer cells while leaving healthy cells in vitro was proven at Purdue University in 1997.

My understanding is that major drug companies have been trying to make a synthetic form of the active agent every since then, but have failed completely.

My suspicion is that the information has been kept close-hold because drug companies cannot make billions on a naturally occurring substance.

Likewise, what successful oncologist or radiologist would want to give up their lucrative practice in order to open up a 'tea shop'?

In the meantime, over half a million Americans die every year from cancer....

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23. Chuch Pelto on August 17, 2010 11:24 AM writes...

TO: noahp
RE: Heh

....I was never able to convince my "colleagues" that my results were anything other than anecdotal. -- noahp

I see that happen ALL THE TIME. And it is one of the reasons I have my 'suspicions' about the 'practice' of medicine being more interested in making money than in saving lives and reducing suffering.

Regards,

Chuck(le)
[What disease did 'cured ham' have?]

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24. Chuck Pelto on August 17, 2010 11:35 AM writes...

TO: Gillespie, et al.
RE: On the Nosy!

What about tageting glycolysis? Maybe Otto Warburg was onto something. No matter how the cancer cells change genetically, they still have to make ATP, and for many reasons, Ox-Phos doesn't cut it for them, while it works in normal cells. -- Gillespie

That's the targeting that the active agent in graviola and pawpaw employ.

The active agent is attracted to something about the cancer cells while passing through the vascular system. It is not attracted to healthy cells. The cancerous cells absorb the active agent which interferes with the Krebs Cycle generation of ATP.

Inside the cell, the active agent 'gums up' the workings of the mitochondria. It's like throwing sugar into a gasoline engine's gas tank. The cancer cells starve to death.

If you know someone who has been told they should adopt hospice care, tell them about graviola and pawpaw. What have they got to lose from drinking some good tea four times a day? At $25-35 a month?

The sooner more people survive, after being told there is no 'hope' for them, the sooner the word of this will spread.

Regards,

Chuck(le)
[If laughter is the best medicine, why isn't it regulated by the AMA?]

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25. PacRim Jim on August 17, 2010 12:11 PM writes...

For selfish reasons it pains me to admit that we remain far too ignorant of human bodies as unique systems of systems. When it comes--and it will come this century--thorough understanding will allow patient-specific therapy. More importantly, real-time systemic monitoring will allow our descendants to escape (or postpone) aging chronic illness. We will have almost made it, if that's any consolation.

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26. partial agonist on August 17, 2010 1:38 PM writes...

"...drug companies cannot make billions on a naturally occurring substance."

At the time of David Newman's 2007 review in J. Natural Products, >60% of all drugs discovered are natural products themselves or were derived from or inspired by them. That number likely hasn't changed a whole lot in 3 years. Trust me, if a pure stable compound works, nobody really cares where it came from, and use patents can be perfectly suitable for reaping the rewards.

I work in cancer, and specifically in targeting cancer cells through their unique metabolic machinery including those that give the Warburg effect. I don't know anything about the graviola and pawpaw mechanistic papers. E-mail me the papers if you want, and I will dig some too.

I hestitate to post my e-mail here- maybe Derek can forward an e-mail to me.

Permalink to Comment

27. partial agonist on August 17, 2010 1:51 PM writes...

I did find a nice review on the paw paw story: Paw Paw and Cancer: Annonaceous Acetogenins from Discovery to Commercial Products,
Jerry L. McLaughlin, J. Nat. Prod. 2008, 71, 1311-1321.

I'm not sure offhand why bullatacin was not developed as a single agent. These molecules disrupt mitochondrial electron transport.

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28. Chuck Pelto on August 17, 2010 2:44 PM writes...

TO: partial agnostic
RE: Pawpaw Papers

You've come across some of what I've found over the last two years, when I first became interested in this matter. Here's the info on graviola, which was first tested at Purdue.

http://www.peruvillage.com/3030/Cancer_purdue.html

Interestingly it was the same McLaughlin. I understand he works elsewhere now. Furthermore, he seems to have found that North American pawpaw, as in 'Indiana Banana', has more of the active agent in it than does graviola.

RE: Heh

Trust me, if a pure stable compound works, nobody really cares where it came from, and use patents can be perfectly suitable for reaping the rewards. -- partial agnostic

I'd like to believe that but too often has my cynicism about the medical industry been confirmed, time and time again. [Note: One has to wonder what the heck is going on in there when ones wife has to show an ER nurse WHERE to apply the electrodes for an EKG. And that's just one of many examples.] It seems to me that, by-and-large, it's all about money these days.

Regards,

Chuck(le)
[Diagnosis: A doctor's forecast of disease based on a patient's pulse & purse. -- The Devil's Dictionary]

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29. Chuck Pelto on August 17, 2010 2:55 PM writes...

P.S. Not sure what you mean by a "pure stable compound". Do you mean extracting the identified 'active agent' in a pure form?

What if it takes more than just THAT for proper action? What if it requires other compounds found in the leaves and stems?

Why wait for a "pure stable compound" when drinking the tea or taking a capsule of the powdered stems and leaves will cure this horrific and family fortune-consuming disorder?

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30. Anon on August 17, 2010 3:05 PM writes...

Wasn't there an ad for the movie Child's Play Sequel named Bride of Chucky that pronounced "Chucky's Back"...

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31. Andy Pierce on August 17, 2010 6:29 PM writes...

Chuck: "The cancerous cells absorb the active agent which interferes with the Krebs Cycle generation of ATP."

Um... the cancer cells are generating ATP primarily by aerobic glycolysis ending in the production of lactate, not the Krebs cycle. That's what the Warburg effect is.

Re: esophageal cancer: Our standard of care is neoadjuvant chemo/radiation, followed by surgery.

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32. Chuck Pelto on August 17, 2010 8:38 PM writes...

TO: Andy Pierce
RE: Thanks...

...for the correction. I was relying on my undergrad studies in biochem for the generation of ATP. That dates back almost 40 years.

Bottom line is that whatever the mechanism is called, the active agent in pawpaw and graviola fouls it up and the cancer cell dies.

Regards,

Chuck(le)
[Rebuke a fool and he will hate you. Rebuke a wise man and he will love you. -- Proverbs]

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33. Anonymous on August 17, 2010 8:40 PM writes...

P.S. About 'standard operating procedures' for esophageal cancer....

Re: esophageal cancer: Our standard of care is neoadjuvant chemo/radiation, followed by surgery. -- Andy Pierce

....wouldn't a nice cup of tea that killed the cancer be better than all THAT stuff?

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34. Chuck Pelto on August 18, 2010 9:07 AM writes...

TO: Andy Pierce
RE: Warburg Education

Thanks for disabusing me on the difference in metabolic process between normal and cancerous cells.

Interesting stuff, that. Might well explain why graviola and pawpaw are 'attracted' to cancerous cells while ignoring normal cells. I'd always been curious as to how that occurred.

Regards,

Chuck(le)
[Research causes cancer in rats.]

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35. partial agonist on August 18, 2010 12:51 PM writes...

Chuck Pelto said: Not sure what you mean by a "pure stable compound".

That's what FDA-approved drugs are and what they must be (or a defined mixture of pure and stable things). It is what the FDA is set up to review. They aren't in the business of approving or even looking at natural mixtures which might vary in composition based upon the time of the year, weather, ripeness of the fruit (if that is what it is from) etc.

If the treatment works, fine. A manufacturer should support a controlled clinical trial, or persuade the NIH to support one, with preliminary hard data. Trials are expensive, but they could theoretically prove that their stuff works. The manufacturers would (I guess) rather rely upon anecdoctal evidence, which seems to live on forever whatever the data. For example, as I recall, several Ginko Biloba clinical trials were run and in all for them it filed miserably (for memory/cognition enhancement). Still you can stroll on over to your local GNC Store and read the bottles and see tons of miracle claims.

We scientists like to see data, and when it is absent we suspect that the money-makers are snake oil salesmen. Why? Because there are lots and lots of snale oil salesmen who capitalize on fears of people who lap up the infomericals like "Miracles Cures that THEY Don't Want You to Know About"

If it works, I want to prove that it works. Period. It's not a matter of monetary gains making me look anywhere else. But I need facts, not stories.

I don't think that drugs targeting the Krebs cycle get a lot of attention because they are bound to be widely toxic, being required for life. Targeting enzymes involved in the glycolytic pathway, though, is a different matter. This is because there are not a whole lot of mostly glycolytic cells, as far as I know: cancer cells, T cells, sperm cells, and smooth muscle cells only when oxygen-deprived.

It's an area where I think discoveries are going to be made, and hopefully not just ones of the type that extend the lives of only a handful of patients, at great expense, for only a few weeks.

Permalink to Comment

36. partial agonist on August 18, 2010 12:53 PM writes...

should have read: "in all of them it failed miserably"

... we need an edit function!

Permalink to Comment

37. Chuck Pelto on August 18, 2010 3:35 PM writes...

TO: partial agnostic
RE: The 'Pure' Stuff

'Pure Stable Compounds': That's what FDA-approved drugs are and what they must be (or a defined mixture of pure and stable things). It is what the FDA is set up to review. They aren't in the business of approving or even looking at natural mixtures which might vary in composition based upon the time of the year, weather, ripeness of the fruit (if that is what it is from) etc. -- partial agnostic

Thanks for elaborating on that.

RE: What 'Scientists' Want

....scientists like to see data, and when it is absent we suspect that the money-makers are snake oil salesmen. -- partial agnostic

Yeah. I've been seeing that a LOT of late. Especially with regards to Anthro-Global Warming. I guess it all depends on what data they wanted to 'see'.

RE: Enough Snake....err....Snark

The way you're describing the situation, I doubt if any of the pharm companies are going to pursue this any more seriously than they have to date, i.e., since the research done 12 years ago. In the meantime, another half-million+ Americans die every year, while their family fortunes are 'eaten alive' by the medical industry. Just like cancer eats away at the body's nutrients.

But, as I said earlier, if someone has been told they've got no hope by their physician...after all the money is gone, insurance or otherwise, they can turn to graviola and/or pawpaw. And should they recover, they'll be living proof of the efficacy. After all....I've SEEN it kill that cancer reported earlier. And, based on the discussion here, I have a better understanding of how it might target cancerous cells while leaving healthy ones alone. The different metabolic processes between the two.

Regards,

Chuck(le)
[I've got Parkinson's disease. And he's got mine.]

P.S. I don't sell graviola or pawpaw. I just report what I've witnessed.

Permalink to Comment

38. gillespie on August 18, 2010 4:19 PM writes...

partial agonist:

It appears we are working on the same project- I am using siRNA to knock out HIF-1a, GLUT-1 and LDH in glioma xenografts in mice, paper in prep. I would be interested in communicating about your favorite glycolytic targets and any papers you have published.

Chuck Pelto- I'm looking into this- if pawpaw is truly a glycolysis agonist, I have a good in vivo modle to test it in.

Permalink to Comment

39. gillespie on August 18, 2010 4:53 PM writes...

This is very interesting- pawpaw inhibits HIF-1a and Glut-1 in vitro
http://pubs.acs.org/doi/pdf/10.1021/np100228d

Permalink to Comment

40. Chemjobber on August 18, 2010 5:26 PM writes...

Hey, Chuck: Aren't you a big homeopathy supporter? Why aren't you suggesting that folks perform serial dilutions of pawpaw?

Permalink to Comment

41. Hap on August 18, 2010 10:11 PM writes...

Perhaps because dilution dilutes his profit, too? Or is that too cynical?

Permalink to Comment

42. Chuck Pelto on August 19, 2010 8:07 AM writes...

TO: gillespie
RE: Homeopathy....

Hey, Chuck: Aren't you a big homeopathy supporter? Why aren't you suggesting that folks perform serial dilutions of pawpaw? -- gillespie

....has it's place. Just like every other form of medical treatment. Indeed. I had a sudden bout of colitis late last week. Didn't recognize it for what it was until I started squeezing out clear jelly. Took the homeopathic materia medica Euphorbia Lathyris. Fifteen minutes later, my large intestine in the vicinity of the appendix didn't feel like it was about to rupture. It had been four days of back-up. Took the better part of this week to finally clear things out and be back to normal.

Pawpaw's action is different from homeopathic techinques. Just like surgery to reset a broken limb is different from pawpaw. There is NO universal panacea in medicine, as far as I've determined from 40 years of looking at it, starting with pre-med microbiology in the late 60s.

If you believe there is a universal cure for all that ails you, please share it.

Regards,

Chuck(le)
P.S. Care to try that little experiment I've mentioned in the past? Or are you afraid you'll discover it actually works?

Only cost about $6. Or are you too strapped for money?

Permalink to Comment

43. Chuck Pelto on August 19, 2010 8:10 AM writes...

TO: gillespie and Chemjobber
RE: Apologies

Sorry for the mis-attribution in the previous article.

Regards,

Chuck(le)
[Seeing my error, through eye-opening coffee, I begin again. -- Haiku error messages]

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44. Chuck Pelto on August 19, 2010 8:17 AM writes...

TO: gillespie
RE:

Chuck Pelto- I'm looking into this- if pawpaw is truly a glycolysis agonist, I have a good in vivo modle to test it in. -- gillespie

Go for it.

But an additional thought. Based on the discussion with partial agnostic and some other comments here, I'd like to see a test done that involved use of the powdered stems and leaves of the plant as well as the supposed active agent in its 'pure stable compound' form.

I suggest this because I suspect that there may be something else in the plant's make-up that affects its efficacy.

RE: Interesting Stuff

This is very interesting- pawpaw inhibits HIF-1a and Glut-1 in vitro. -- gillespie

Thanks for the link. I've added it to my collection of information relating to graviola and pawpaw.

Regards,

Chuck(le)
[Reading is thinking with someone elses mind.]

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45. Chuck Pelto on August 19, 2010 12:20 PM writes...

TO: Hap
RE: [OT] Heh

Perhaps because dilution dilutes his profit, too? -- Hap

If you knew what you were talking about, i.e., homeopathy, you'd know that the more you dilute the MORE the 'profitability'....based on contemporary models of such.

Hope that helps....

Regards,

Chuck(le)
[Stupid, adj., Ignorant and proud of it.]

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46. Chuck Pelto on August 19, 2010 1:32 PM writes...

TO: gillespie, et al.
RE: That Report....

....you thankfully linked to, seems to indicate that the efficacy of pawpaw in killing cancer is no different from the 'pure stable compound' vis-a-vis the powdered stems and leaves.

The question becomes.....

....why bother with refinement?

The unrefined, i.e., less expensive to produce, product is just as effective in killing cancer cells, while leaving healthy cells alone.

Again! Pharm companies lose. Tea-shops win.

Regards,

Chuck(le)
P.S. So....

....how come there's been no great 'revelation' of a 'cure' for cancer?

P.P.S. I see these "Race for the Cure" advertisements and I just have to shake my head in sorrow. If they ONLY 'knew'.....

P.P.P.S. And before anyone starts thinking "Conspiracy Theorist", be advised.....

.....I know a retired US Navy officer who KNEW that the Gulf of Tonkin Incident, as reported by then SecDef MacNamara and then President Johnson, was a lie. He and all the other officers at CINCPAC. He admitted to it to a group of fellow Mensans after MacNamara's book came out, at a watering-hole after the monthly General Meeting of the Denver chapter. So don't tell me there are no such thinks as 'conspiracies'. He and his ilk kept their 'code of silence' for 25 years. And at what cost? Try 58,000 American dead and 2-4 million Southeast Asians dead too.

But, considering that we knew about graviola since 1997 and we've not had the 'cure' widely available YET....at 550K every year.....YOU do the math....

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47. Chuck Pelto on August 19, 2010 1:36 PM writes...

P.S. If any of you in the professional-research field encounter what we in the Army intel field refer to as 'resistance'....

....three guesses....as to why.

First two don't count.

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48. Jesse on September 10, 2010 3:10 AM writes...

Cancers are a stunning example of evolution-in-action, but there's one big difference compared with infectious organisms.

The infectious organism gets to pass its accumulated wealth of adaptations, to be enriched further by each successive generation.

Each patient's cancer starts the evolutionary clock back at zero. A cancer will possess a landscape of escape paths of various probability, with each patient's case navigating a subset of those paths.

With each generation (of patients, researchers, and therapeutics), we'll have a better set of roadblocks set-up in anticipation, a little further down the road.

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49. Ute Colafrancesco on January 7, 2013 4:20 PM writes...

Only wanna say that this is very helpful , Thanks for taking your time to write this.

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