[Herodotus38]

How about cell cultures that are induced with viral vectors to become cancerous by the introduction of an oncogene? Do you think there is a difference in metabolism in the cells that become tumorigenic after transfection? If so why does it happen with introduction of an oncogene but not in the control vector when they have identical cell culture media/nutrients?

[238475235243]

My bet is because more than one thing happens (some insult to the mitochondria in parallel, say) and/or because the gene is actually expressing something metabolic we don't understand. Seyfried (I think) actually points out the parallel metabolic influence of some therapies that we think are working genetically.

[Herodotus38]

So if the gene, which is DNA, is expressing something that changes the metabolism, doesn’t that mean a change in DNA is ultimately responsible?

Edit: also if you could introduce a change in the cells that only changed the metabolism and didn’t alter DNA you could prove your theorem if you then caused them to be tumorigenic.

[sooheon]

Of course you're right, and that's why the role of DNA in cancer is undeniable. It's possible to argue (what Warburg did in the 1920s) that insult to mitochondria can kick off cancer, but it's almost impossible to maintain that this can occur and progress into malignant cancer without somatic mutations being involved at some point. Without encoding to DNA, how will the cancer continue to behave malignantly across cell generations? A mutation free cancer cell is an oxymoron.

[238475235243]

Yes and no, because it changes how you think about it.

If it's "just DNA" then we should focus on relevant therapies. But this is what we've done for 60 years and it hasn't gotten us very far. In fact depending on how you slice the numbers we've made almost no progress since chemo was "invented".

On the other hand if it's mitochondria and DNA damage is just one possible route, and damage happens all the time, then there are metabolic approaches. These include simple diet changes, metformin and all kinds of other things.

We need to abandon the "just DNA" paradigm. Epigenetics is far bigger than most understand, and DNA is far more malleable than most people know.

As both books (I think) say, the TCGA project was largely a failure for exactly these reasons: DNA is a big moving target and the cell-to-cell variance is very large.

[Herodotus38]

There is a cancer called CML, it used to be fatal, now there are targeted chemotherapies that work by inhibiting a tyrosine kinase. The test for the cancer is detecting the fusion gene Bcr-Abl. People with CML take a pill daily that targets the protein that is made by that abnormal gene.

The DNA paradigm explains this very well. How does the book explain this treatment?

How about a stem cell transplant? Why do they cure certain cancers? Does the metabolism of the person donating their stem cells get taken up and adopted permanently by the recipient?

[238475235243]

This is very tiring, and I mean that in a kind way. Honestly, whoever you are.

Let's look at the first Wikipedia sentence on tyrosine kinase as a starting point:

"A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell."

What's ATP? We both know what ATP is. Is ATP deeply part of metabolism? We both know it almost is a definition of metabolism. I want to shout at you. But I don't know who you are or how to connect with you.

Please, for the love of anything that you find Holy, instead of arguing with me on the internet do this: Read the books I recommended, and start looking for the links to metabolism like I just did for you instead of trying to "see DNA everywhere". You will go so much further and help all of us than just arguing with me.

[Herodotus38]

I mean it in good faith, and I am just trying to challenge how throwing out the dna paradigm explains things better. I agree that metabolism plays an important role in cancer, and we don’t fully understand it. But, I take issue with your original claim that the current paradigm is wrong because it explains things that I have personally seen in the lab when I did lab workup, in my clinical work and in my family members who have cancer and are being treated with medications that work.

As to the atp issue, yes it is involved with metabolism but so so much more. If you have time read The Biology if Cancer by R A Weinberg. He does a good job of exploring the historical investigations as wellas the science.