understanding cancer

[nec209]

We know that cancer is cells in the body are malfunctioning and going bad.They are different than viruses has viruses has to go into the body.But Cancer spreads and replicate like a viruses.The only diiferent is a viruses has to go in your body.Well Cancer is cells in the body are malfunctioning and going bad .

 

Cancer is a leading cause of death -- according to the World Health Organization, 12.5% of all deaths worldwide.

 

There is much research into how to treat it or why some people get cancer and other people don't .But all diseases like cancer or viruses seem to be on the rise.

 

My views are food or drugs are why we have cancer .And chemotherapy or surgery seems to be the only option to kill cancer .

 

We know that cells tell other cells what to do .Why can't we fight way to tell cells to kill the bad cells?

 

Why are cells going bad and replicate ? We know some foods and drugs lead to cancer but we do not know why.

[nec209]

My views are food or drugs are why we have cancer .

 

We know some foods and drugs lead to cancer but we do not know why

 

I'm going to remove the above but cannot edit the old thread.The above will lead to a debade.

[insane_alien]

well this is a debate forum, we like debate. why would you want to remove debate?

[ennui]

Cancer is a tricky subject, and it's hard to appreciate the hows and whys without a background in the subject.

 

First of all, cells need to replicate. Cells are being damaged all the time by internal causes (i.e. the oxygen species produced by the mitochondria) and also from external causes (U.V., mechanical damage, etc). Your whole digestive system works on the principle of shedding layers of cells (epithelium) whenever you swallow food. So replicating cells are not bad - this is, after all, how you developed as an embryo!

 

Usually the body has various check-points in the cell cycle to make sure that the cells aren't misbehaving. So when they're replicating & dividing, they have a whole host of proteins to check that the cell isn't cancerous. You might have heard of the notorious p53 gene. It codes for a protein that is a major tumour suppressor.

 

Say, for instance, that your cell's DNA has been damaged and it hasn't been repaired. Your cell wants to divide. This could lead to a very bad situation: the DNA damage could mean that the cell will go haywire and produce cancerous cells. It wouldn't replicate the genome properly, and the daughter cells would be aberrant.

 

It's thanks to p53 and other tumour suppressor genes that the cell doesn't divide uncontrollably. p53 and other proteins arrest the cell cycle, stop it from dividing, and prevent carcinogenesis. There are a whole network of these proteins whose pathways resemble the London tube map - it's a complex network. It's when these tumour suppressors fail that cancer comes about.

 

You're very right that some cells tell other cells what to do. Cell signalling is another facet of cancer. Cells need growth factors to tell them when to grow, makes sense right? Well, if you have a mutation in a growth factor receptor (i.e. HER2, found in breast cancer cases) that means it's on all the time, even when you don't need it to be, then you're going to get cells thinking they need to grow and divide when they don't need to be. You might get cancer if the body doesn't deal with it.

 

You can probably see that this is a big, complicated subject. Lots of different things can lead to tumourigenesis.

 

I don't think that food and drugs/pharmaceuticals are a big part of why we get cancer. The bigger culprits are things like smoking, sun exposure and many more besides. I can't think of any ordinary pain-killer which has been linked to cancer in epidemiological studies!

 

Yes, certain everyday foods do contain carcinogens. It's surprising to think that even everyday foods like parsley, pepper, and other vegetables contain mutagenic compounds that can damage DNA. These have been identified through experiments like the AMES test.

 

But this doesn't mean that ordinary foods really cause cancer: as I've shown above, the body has a good mechanism for repairing DNA damage. It's when you over-do it (by smoking, for instance) that the body simply can't cope with all the cellular damage and cancer might come about. A healthy diet is wonderful - but diets with high fat content have been linked to colon cancer, and excessive alcohol consumption has been linked to oral cancers. Excess is the thing to be avoided. If you want to learn more about how these foods are linked to cancer, try doing a search in Pubmed.

 

At the moment a lot of research is going into developing drugs to target the pathways leading to cancer. As an example, drugs are being designed to inhibit the growth receptors that in some breast cancers lead to cells dividing uncontrollably. But research is limited because something that might work in the test-tube might not work in a human body.

 

Human genetics is a wonderful and fascinating area, but even some basic things are still unknown, such as the organisation of chromatin at higher levels. New kinases are being discovered all the time. Imagine trying to repair a broken down car without having a full idea of what an engine looks like, or how it works. Cancer is a enormous field - 1000s of things can go wrong and lead to cancer. To fund one ordinary PhD project to study just one of these pathways (and a small part of it, at that) would cost around £90,000. You should now be able to easily imagine how the money can go quickly.

 

So we have a good idea of why certain things cause cancer. Cancers might be on the rise because of lifestyle. Every summer I see people on the beach without appropriate sun-screen, and I still see teenagers smoking. So I wouldn't be so quick to blame things like drugs. A lot of great research is happening to develop pharmaceuticals to combat cancer, and if you don't think progress is happening quickly enough, donate to your local cancer charity to fund some research!

Edited March 3, 2009 by ennui

[nec209]

First of all, cells need to replicate. Cells are being damaged all the time by internal causes (i.e. the oxygen species produced by the mitochondria) and also from external causes (U.V., mechanical damage, etc). Your whole digestive system works on the principle of shedding layers of cells (epithelium) whenever you swallow food. So replicating cells are not bad - this is, after all, how you developed as an embryo!

 

Usually the body has various check-points in the cell cycle to make sure that the cells aren't misbehaving.

 

We do not want to stop cells that replicate only the bad cells that replicate .Sure cells have to replicate and divide to replace the dead cells or damaged cells.

 

But you say the DNA in the cell tell the cell how to replicate or divide ?And the DNA in the cell does the various check-points ?

 

When a cell is misbehaving what is it doing and why can't the DNA fix it?

 

 

So when they're replicating & dividing, they have a whole host of proteins to check that the cell isn't cancerous. You might have heard of the notorious p53 gene. It codes for a protein that is a major tumour suppressor.

 

 

But the cells need protein to live .How can the protein be bad ?

 

Say, for instance, that your cell's DNA has been damaged and it hasn't been repaired. Your cell wants to divide. This could lead to a very bad situation: the DNA damage could mean that the cell will go haywire and produce cancerous cells. It wouldn't replicate the genome properly, and the daughter cells would be aberrant.

 

This what I do not understand how can the cells DNA get damaged? And how can the DNA fix it self?

 

Some people can have bad food and smoke every day for 70 years and have no problem some people cannot do this for 10 years.

 

Your body is so conplex and everyone is different.

 

Anyways I will reply to your other posts soon.

[ennui]

The cell cycle is controlled by lots of factors, like cyclins and cyclin-dependent kinases (CDKs). These are proteins which use phosphorylation to control things like protein synthesis, and also to allow the cell to progress through the stages of mitosis. And these proteins are usually always basally transcribed, and rise temporally when the cell needs to divide.

 

In regards to DNA being able to fix things: if a cell is not responding to death-signalling to induce apoptosis (e.g. Fas receptor signalling) then it most likely has a mutation in one of the pathways. The DNA might not be able to fix this, because the tumour suppressor genes themselves could have a mutation.

 

DNA is damaged thousands of times each day, and while we have a lot of mechanisms for DNA repair (e.g. non-homologous end joining/NHEJ or single-strand excision/BER) the system is not perfect. As we age, mistakes inevitably happen in DNA replication. So while we might have two copies of a certain tumour-suppressor gene; as mutations might be introduced in time, the copy-number of the protein product is no longer sufficient to perform its function, and a cancerous phenotype arises.

 

Yes, cells need proteins to survive. But mutations in proteins are largely responsible for a lot of different cancers. The most notorious is arguably mutations in Ras - a protein involved in receptor tyrosine kinase receptor signalling. Any one of three point mutations (refer to my previous paragraph of mutations happening in the genome) will render it constitutively active, resulting in the transcription of proteins which lead to cell division, growth and angiogenesis.

 

DNA is damaged by a huge number of causes. If you're familiar with DNA structure, you'll know that it's a sugar-phosphate backbone with bases attached to them, projecting into the equatorial of the helix. Chemical bonds can be broken or made if energy is provided, this will overcome the energy barrier necessary for another reaction. Now imagine you have a very high-power X-ray hitting a molecule of DNA.. what do you think will happen? The likelihood is that it will shear the DNA and result in a double-strand break. Other kinds of can cause the bases to be modified, so that the RNA polymerase and DNA polymerase make mistakes. It changes the DNA so that its shape changes, or so that the wrong base is replicated.

 

Your last question repeats your first one, which I outlined above. DNA can repair itself through evolved pathways such as NHEJ and BER. Proteins recognise the break, and use their helicase/polymerase tools in order to fix it. If you're lucky, they can form a Holloday junction and use the homologous strand to fix the damaged one. But obviously this won't work in double-strand breaks.

 

Yes, everyone is different and has different DNA. That's natural variation. But people all have the same DNA repair mechanisms. The reason why some people can smoke for 70 years and not get lung cancer is because they have "good genes" (forgive the crude term) or just luck. If you blindfold people and make them cross a road 10 times, by statistical possibility some people will cross safely for 10 times. Smoking doesn't guarantee cancer, it just significantly raises the risk.

[nec209]

What I'm having a hard time to understand is tumorigenesis and why some proteins are bad.

 

When the cell mutated or deregulated why can't the proteins function properly .Why is the protein different.

 

Why can't they make a protein inhibitor they do it with HIV protease .

[ennui]

I've answered these questions in my last two posts. What I think might help is if I use a hypothetical example.

 

The central dogma in biochemistry is that DNA produces mRNA, which in turn produces a protein. So the scheme is:

 

DNA [math]\leftrightarrow[/math] mRNA [math]\rightarrow[/math] Protein

 

You'll notice that arrow linking DNA to mRNA goes two ways. This is because there's transcription and reverse transcription (such as in viruses).

 

Let's invent a protein. We'll call it 'SFN'. This protein is a growth receptor on the plasma membrane. When a hormone hits it, the cell knows when to divide and grow. So if SFN was active all the time, the cell would divide exponentially. You'd get cancer.

 

This is the gene for SFN:

 

5'-ATGCGACCCTCCGGGACGGCC-3'

 

This is the protein it will produce:

 

N-MRPSGTA-C

 

Now imagine that this protein needed the R residue (arginine, I've underlined it) to bind a hormone and let the cell know when to grow and divide.

 

If the DNA is exposed to damage (from U.V., oxygen, carcinogens found in cigarettes, or whatever) then there could be a mutation. The "CGA" part of the DNA (this codes for the arginine in the protein) could become CCA. What will this do? It will change the protein. Instead of getting an arginine as the second amino acid, you'll now get a proline. The protein now has a different shape.

 

What does this mean? It means that now the protein doesn't have the right amino acid to bind the hormone. It's no longer controlled by the body and the endocrine system. The result is that it's active all the time. It will result in a cancerous cell.

 

This is a simplified analogy. The sequence is actually from a real protein, EGFR1, which is hugely present in a LOT of cancers. The cell can normally cope with mutation events like this through repair mechanisms. But as we age (and as we're exposed to more mutagenic chemicals) we lose the 'safety nets' that our cells have evolved. The damage we get is cumulative.

 

I hope this helps you to understand. And I'll repeat the sentiments from my first post: if you don't think that progress is happening fast enough, get involved in the field and help out.

Edited March 16, 2009 by ennui

[zewel]

I've answered these questions in my last two posts. What I think might help is if I use a hypothetical example.

 

The central dogma in biochemistry is that DNA produces mRNA, which in turn produces a protein. So the scheme is:

 

DNA [math]\leftrightarrow[/math] mRNA [math]\rightarrow[/math] Protein

 

You'll notice that arrow linking DNA to mRNA goes two ways. This is because there's transcription and reverse transcription (such as in viruses).

 

Let's invent a protein. We'll call it 'SFN'. This protein is a growth receptor on the plasma membrane. When a hormone hits it, the cell knows when to divide and grow. So if SFN was active all the time, the cell would divide exponentially. You'd get cancer.

 

This is the gene for SFN:

 

5'-ATGCGACCCTCCGGGACGGCC-3'

 

This is the protein it will produce:

 

N-MRPSGTA-C

 

Now imagine that this protein needed the R residue (arginine, I've underlined it) to bind a hormone and let the cell know when to grow and divide.

 

If the DNA is exposed to damage (from U.V., oxygen, carcinogens found in cigarettes, or whatever) then there could be a mutation. The "CGA" part of the DNA (this codes for the arginine in the protein) could become CCA. What will this do? It will change the protein. Instead of getting an arginine as the second amino acid, you'll now get a proline. The protein now has a different shape.

 

What does this mean? It means that now the protein doesn't have the right amino acid to bind the hormone. It's no longer controlled by the body and the endocrine system. The result is that it's active all the time. It will result in a cancerous cell.

 

This is a simplified analogy. The sequence is actually from a real protein, EGFR1, which is hugely present in a LOT of cancers. The cell can normally cope with mutation events like this through repair mechanisms. But as we age (and as we're exposed to more mutagenic chemicals) we lose the 'safety nets' that our cells have evolved. The damage we get is cumulative.

 

I hope this helps you to understand. And I'll repeat the sentiments from my first post: if you don't think that progress is happening fast enough, get involved in the field and help out.

it is very very fantastic topic

but i have question

i know that every receptor have a specific hormone or specific protein

to bind in it as lock and Kay theory and these means that

the wrong protein (that come from mutation in DNA)can not bind with the receptors or what

[georgeskohler]

Going back to the question about targeting cancer cells--as written in previous posts here, in many cancers, the cancer cells express a certain protein (for example EGFR) to much higher levels than normal cells. A lot of research related to targeting tumor cells selectively has focused on monoclonal antibodies--such an antibody might bind specifically to EGFR, reducing the expression of the receptor/preventing it from dimerizing/preventing it from binding growth factor.

 

I think the question about causes of cancer is also interesting. Viruses can also cause cancer, like HPV causes cervical cancer, and there is a vaccine for that.

 

Yes, it is true that some people are more susceptible to cancer than others. In some cases there is a very clear genetic component--for example, it is more likely that someone who inherits a mutated copy of the Rb gene from one parent will acquire a mutation in the other gene, leading to retinoblastoma, than it is that someone who inherits two normal copies will acquire two mutations and end up with this condition.

 

Of course diet and lifestyle are also important, and there is a clear correlation between trends in smoking and lung cancer incidence, and between the advent of refridgeration and the occurrence of gastric cancer. But an individual's genetic makeup will play a large role in determining whether one can smoke for 40 years and not get lung cancer.

 

About the question of why can't we tell cells to kill bad cells, that's interesting. One of the main jobs of natural killer cells and cytotoxic T cells is to kill cells that are infected with viruses or bacteria; they can also kill tumor cells but tumor cells can evade being detected as well.