Cancer DNA is detectable in blood years before diagnosis

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biotechbio ◴[18 Jul 25 20:54 UTC] No.44609723[source]▶

Some thoughts on this as someone working on circulating-tumor DNA for the last decade or so:

- Sure, cancer can develop years before diagnosis. Pre-cancerous clones harboring somatic mutations can exist for decades before transformation into malignant disease.

- The eternal challenge in ctDNA is achieving a "useful" sensitivity and specificity. For example, imagine you take some of your blood, extract the DNA floating in the plasma, hybrid-capture enrich for DNA in cancer driver genes, sequence super deep, call variants, do some filtering to remove noise and whatnot, and then you find some low allelic fraction mutations in TP53. What can you do about this? I don't know. Many of us have background somatic mutations speckled throughout our body as we age. Over age ~50, most of us are liable to have some kind of pre-cancerous clones in the esophagus, prostate, or blood (due to CHIP). Many of the popular MCED tests (e.g. Grail's Galleri) use signals other than mutations (e.g. methylation status) to improve this sensitivity / specificity profile, but I'm not convinced its actually good enough to be useful at the population level.

- The cost-effectiveness of most follow on screening is not viable for the given sensitivity-specificity profile of MCED assays (Grail would disagree). To achieve this, we would need things like downstream screening to be drastically cheaper, or possibly a tiered non-invasive screening strategy with increasing specificity to be viable (e.g. Harbinger Health).

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1. zaptheimpaler ◴[18 Jul 25 22:36 UTC] No.44610539[source]▶

>>44609723 #

I guess the problem is a mismatch between detection capability and treatment capability? We seem to be getting increasingly good at detecting precancerous states but we don't have corresponding precancer treatments, just the regular cancer treatments like chemo or surgery which are a big hit to quality of life, expensive, harmful etc.

Like if we had some kind of prophylactic cancer treatment that was easy/cheap/safe enough to recommend to people even on mild suspicion of cancer with false positives, we could offer it to positive tests. Maybe even just lifestyle interventions if those are proven to work. That's probably very difficult though, just dreaming out loud.

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2. pas ◴[19 Jul 25 00:43 UTC] No.44611466[source]▶

>>44610539 (TP) #

do the chemo medications not do anything useful at low(er) doses in these precancerous situations?

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3. amy_petrik ◴[19 Jul 25 01:17 UTC] No.44611649[source]▶

>>44610539 (TP) #

>I guess the problem is a mismatch between detection capability and treatment capability?

the problem is you do the test for 7 billion people, say, 30 times over their life... 210000000000 tests. imagine how many false negatives and false positives, the cost of follow up testing only to find... false positive. the cost of telling someone they have cancer when they don't. the anger of telling someone they are free of cancer, only to find out they had it all along

this tech isn't that good, nowhere near it, more like a 1 in 100 or 10 in 100 rate of "being wrong". those numbers can get cheesed towards more false positives or false negatives.

as for grail, they tried to achieve this and printed OK numbers... ... .. but their test set was their training set. so the performance metrics went to shit when they rolled it out to production

4. m463 ◴[19 Jul 25 02:13 UTC] No.44611948[source]▶

>>44610539 (TP) #

People are routinely notified they are pre-diabetes.

It gives people the agency to alter their lifestyle trajectory.

I personally suspect that people get and cure cancer all the time.

I wonder if cancer is just damage to your body - either a lot of direct damage or interfering with the body's ability to manage/heal itself.

if someone was pre-cancer, would it help to exercise, cut out sugar, use the sauna, stop overeating? I'll bet it might make a difference

5. voiprodrigo ◴[19 Jul 25 02:33 UTC] No.44612054[source]▶

>>44611466 #

I think chemo in general kills rapidly dividing cells, which is a characteristic of cancer cells and, unfortunately, many types of regular cells as well, hence many of the side effects, like hair loss. If it is precancerous, then probably it’s not yet dividing in that way, so probably wouldn’t make much of a difference, unless you’d actually catch the moment when the switch to full fledged malignant happens.

6. marcosdumay ◴[19 Jul 25 03:45 UTC] No.44612413[source]▶

>>44610539 (TP) #

Weren't the mRNA vaccines created exactly for that?

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