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One Drug to Shrink All Tumors

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Re: One Drug to Shrink All Tumors

#31

Post by suprgeek »

antihero wrote: post #26
suprgeek wrote: post #16

This is basically a neat hack - Cancerous cells use a certain Chemical marker to stop being attacked. This researcher blocks this marker from being used thus allowing the body's immune system to attack and destroy the Cancerous cells. This is very promising research indeed but while they have shown Human Tumor Cells in mice shrinking, they have yet to show Human cells in Humans shrinking. Should make for a very cool…

Isn't this marker also used by healthy cells? So what is to stop your system basically attacking itself massively?

I think the key is that Cancerous cells expressed a higher level of this marker leading the Immune cells to destroy them specifically.

However there is also this line "Although macrophages also attacked blood cells expressing CD47 when mice were given the antibody, the researchers found that the decrease in blood cells was short-lived; the animals turned up production of new blood cells to replace those they lost from the treatment," so this seems like a very valid concern.

Re: One Drug to Shrink All Tumors

#32

Post by Udo »

siganakis wrote: post #24
frisco wrote: post #9

Wow. Extraordinary claims require extraordinary evidence, but Irv Weissman and his lab are the real deal. Here's the original article (which is open access): http://www.pnas.org/content/early/2012/03/20/1121623109 Of course, this isn't the first time we've seen such promising initial results only to hit roadblocks in translation, but here's to hoping it's a real effect, even if it eventually turns out to be less than…

The trouble is that there are many, many different ways that a cancerous cell is able to be cancerous. A malignant cancer cell has generally had upwards of 7 mutational events that directly enable it to replicate itself enough times to form a tumor and become damaging. These mutations includes things like breaking programmed cell death (apoptosis) pathways (e.g. P53 mutations), increases in anaerobic glycolysis (due…

Yes, however, the "drug" described (it's more of an idea for a drug at this stage, really) does not aim to disrupt the tumor cell itself. Instead it's based on the observation that many (maybe most?) cancerous cells over-express the protein CD47 on their surfaces as a survival mechanism in order to prevent macrophages and dendrites from taking them out.

If successful - and that's a big if, because I'd be willing to wager this treatment will never see the light of day - if successful, the drug would break the CD47 recognition mechanism by blocking the protein with antibodies, thereby allowing the patient's immune system to attack the malfunctioning cells. In a way this would be more elegant than aiming at re-starting apoptosis pathways or blocking the expression of angiogenesis factors because the specific mechanisms employed by cancer cells to do so seem to vary greatly as you said.

Re: One Drug to Shrink All Tumors

#33

Post by Udo »

wensing wrote: post #11

Why is it that I've read maybe a dozen articles like this in the past couple of years but still don't see much change in the way cancer is being treated in the wild? Will there be a year in the not-too-distant future when all of these breakthroughs finally hit the shelves? I realize the answer is "clinical trials take time and don't always work" but can someone please explain the process to me?

Most of these grandiose announcements are composed in a way to secure funding for the research group releasing the paper in question. They are almost always entirely based on idealized animal models that have no hope of ever working in the real world. A very small percentage of these research ideas is viable and does make its way to clinical trials, after which these ideas are almost certainly buried never to be seen again due to a crushing load of patent concerns, hedging of liabilities, conflicts with corporate strategies, and general cultural resistance.

Pharmaceutical companies are doing a difficult tight rope walk here. On the one hand, they have a nice status quo, in essence a license to print money. On the other hand, they are subject to a number of threatening forces such as the expiry of patents or the ever-present danger of a rogue competitor making a disruptive discovery. This means there has to be a certain amount of innovation, and that innovation has to cost a lot of money, but ideally the improvements would be minimal. A lot of times, it makes way more sense to kill an idea and keep it under wraps. All big companies have to make these kinds of decisions, it's just good business sense.

Re: One Drug to Shrink All Tumors

#34

Post by mietek »

Gatsky wrote: post #29
wensing wrote: post #11

Why is it that I've read maybe a dozen articles like this in the past couple of years but still don't see much change in the way cancer is being treated in the wild? Will there be a year in the not-too-distant future when all of these breakthroughs finally hit the shelves? I realize the answer is "clinical trials take time and don't always work" but can someone please explain the process to me?

Cancer is a difficult biological problem. It is probably the most difficult biological problem I can think of, being both microscopic and inscrutable but also sharing features of population-scale problems. We use cancer as an analogy, but what is an analogy for cancer, apart from humanity itself? It is easy to forget that most cancers develop through an evolutionary process that takes 15 - 20 years. During this time…

There is just one more difficult biological problem; namely, death.

Re: One Drug to Shrink All Tumors

#35

Post by pja »

wensing wrote: post #11

Why is it that I've read maybe a dozen articles like this in the past couple of years but still don't see much change in the way cancer is being treated in the wild? Will there be a year in the not-too-distant future when all of these breakthroughs finally hit the shelves? I realize the answer is "clinical trials take time and don't always work" but can someone please explain the process to me?

You read many articles like this because the press likes to latch onto every research finding and shout "Drug X / Prof Y cures cancer!"

In reality, cancer is many, many different diseases. About the only thing that cancers share is the property of uncontrolled (and unwanted) growth. Some of these cancers we already know how to cure, others remain incurable to date.

The reality is probably that there is no "cure for cancer", rather there are many, many individual treatments for specific cancers. Eventually, we may be able to tailor treatments to individual cancers but that's a long way away at the moment as I understand things.

"The Emperor of All Maladies" is a good read on the subject.

Re: One Drug to Shrink All Tumors

#36

Post by refurb »

vibrunazo wrote: post #15

Anyone familiar with these could share some estimate of in about how much time can we expect to hear the results from human trials?

Before even starting human trials they would need to do a bunch of pre-clinical work (pharmacokinetics, toxicology, etc). They could then get permission from the FDA to start phase I trials, which, depending on the type of cancer tested on, would probably take a couple years to turn around and get data on.

My guess? 4-5 years?

Re: One Drug to Shrink All Tumors

#37

Post by jballanc »

Udo wrote: post #32
siganakis wrote: post #24

Earlier quoted context omitted.

The trouble is that there are many, many different ways that a cancerous cell is able to be cancerous. A malignant cancer cell has generally had upwards of 7 mutational events that directly enable it to replicate itself enough times to form a tumor and become damaging. These mutations includes things like breaking programmed cell death (apoptosis) pathways (e.g. P53 mutations), increases in anaerobic glycolysis (due…

Yes, however, the "drug" described (it's more of an idea for a drug at this stage, really) does not aim to disrupt the tumor cell itself. Instead it's based on the observation that many (maybe most?) cancerous cells over-express the protein CD47 on their surfaces as a survival mechanism in order to prevent macrophages and dendrites from taking them out. If successful - and that's a big if, because I'd be willing to w…

Unfortunately, evolution is evolution, and if there is any way that cancer cells can trick the immune system that does not require CD47, trust me we'll know about it after the first few months using this drug. We've probably learned more about the intricate inner workings of cells by studying the ways in which cancers can evade treatments than by any other method. Still, I don't doubt this will be another tool in the oncologists tool belt and likely a useful one at that.

Is cancer cured? Not by a long shot!

What I find mildly disappointing is that cancer is an evolutionary process, but it is still treated primarily as a cell signaling disease. That is, everyone is studying how to attack individual cells. What we really need is a better understanding of the evolutionary process as a whole. Combination treatments are likely the correct solution, but which ones? in what doses? with what timing? Those are questions we need to answer.

Re: One Drug to Shrink All Tumors

#38

Post by tomkin »

pja wrote: post #35
wensing wrote: post #11

Why is it that I've read maybe a dozen articles like this in the past couple of years but still don't see much change in the way cancer is being treated in the wild? Will there be a year in the not-too-distant future when all of these breakthroughs finally hit the shelves? I realize the answer is "clinical trials take time and don't always work" but can someone please explain the process to me?

You read many articles like this because the press likes to latch onto every research finding and shout "Drug X / Prof Y cures cancer!" In reality, cancer is many, many different diseases. About the only thing that cancers share is the property of uncontrolled (and unwanted) growth. Some of these cancers we already know how to cure, others remain incurable to date. The reality is probably that there is no "cure for c…

I used to think that, until I watched the TED talk by William Li [1]. The process of angiogenesis can be found as the catalyst in every cancer and medicine/food already work to reverse or halt angiogenesis. Doxycycline, for example, is a broad-spectrum anti-biotic that has been around for decades, is cheap and readily available and has been successful at slowing or regressing tumors. [2]

[1] http://www.ted.com/talks/william_li.html

[2] http://www.sunridgemedical.com/ResearchArticles/DoxycyclineC... (PDF)

Re: One Drug to Shrink All Tumors

#39

Post by bedris »

antihero wrote: post #26
suprgeek wrote: post #16

This is basically a neat hack - Cancerous cells use a certain Chemical marker to stop being attacked. This researcher blocks this marker from being used thus allowing the body's immune system to attack and destroy the Cancerous cells. This is very promising research indeed but while they have shown Human Tumor Cells in mice shrinking, they have yet to show Human cells in Humans shrinking. Should make for a very cool…

Isn't this marker also used by healthy cells? So what is to stop your system basically attacking itself massively?

Good question. I'm an author on both of the new CD47 studies, so I'll try to answer this for you:

1. CD47 appears to be higher on tumor cells than on normal cells. In general, the higher the expression of a marker on a diseased cell versus a healthy cell, the more of a therapeutic window/index [1] that is available for a treatment to specifically target diseased cells.

2. Inhibiting the anti-phagocytosis (i.e., "don't eat me") signal is only half of the equation. There are also pro-phagocytosis (i.e., "eat me") signal(s) that also are present [2] and that play a role in whether, and how well, macrophages, and other phagocytes, can phagocytose a cell. "Eat me" signal(s) also differ between normal and cancer cells, adding more nuance to the situation.

[1] Therapeutic index: http://en.wikipedia.org/wiki/Therapeutic_index

[2] A paper examining a putative "eat me" signal, as it relates to CD47: http://stm.sciencemag.org/content/2/63/63ra94.abstract

Re: One Drug to Shrink All Tumors

#40

Post by Symmetry »

frisco wrote: post #9

Wow. Extraordinary claims require extraordinary evidence, but Irv Weissman and his lab are the real deal. Here's the original article (which is open access): http://www.pnas.org/content/early/2012/03/20/1121623109 Of course, this isn't the first time we've seen such promising initial results only to hit roadblocks in translation, but here's to hoping it's a real effect, even if it eventually turns out to be less than…

Wait, how is this claim extraordinary? There's a proposed mechanism that doesn't seem to contradict anything we had previously thought we knew about biology, its not like researcher is claiming that he's found evidence for Lamarkian evolution or something.

We ask for extraordinary evidence for claims that are in and of themselves extraordinary. Simply having extraordinary implications doesn't warrant needing extraordinary evidence, though we should always be hesitant to rely on one person's experiments whether their claims are ordinary or not.

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