Bucweey34,
Thank you for sharing the case of ctDNA readings for the patient, some comments below:
Why ctDNA data is so important: I am not pretending to contribute here something new (this all has been said before), this is just a reminder of the upcoming October data that we will likely receive containing ctDNA measurements following the context of the latest poster. You can call it a “bootstrap” if you like.
ctDNA is called a liquid biopsy because it lets doctor's “biopsy” a tumor using a simple blood (liquid) draw instead of cutting into tissue.
That’s the core idea — but here’s the deeper reasoning:
1. It captures tumor DNA directly from blood: Tumors constantly shed small fragments of DNA into the bloodstream. These fragments, circulating tumor DNA (ctDNA) carry the same mutations found in the tumor itself.
A blood sample containing ctDNA is therefore a biological snapshot of the tumor, just like a tissue biopsy.
2. It replaces or complements surgical tissue biopsy requiring: needles/endoscopy/surgery/anesthesia, the biopsy comes from blood (a liquid), not solid tissue.
3. It can be repeated frequently: tissue biopsies can’t be done every week. But ctDNA can be measured: weekly/biweekly/monthly, you can track tumor response in real time.
4. It detects microscopic disease, ctDNA can reveal: minimal residual disease (MRD), early relapse, treatment response, resistance mutations.
Often weeks or months before scans, which is why ctDNA decline is such a powerful early biomarker.
5. It reflects the whole tumor burden: a tissue biopsy samples one spot. ctDNA comes from all tumor sites, primary tumor + metastases because all shed DNA into blood.
This gives a more complete picture of tumor biology.
Now, because ctDNA is a direct, quantitative measurement of total tumor burden, it drops immediately when tumors die and rises immediately when tumors grow. ORR and RECIST shrinkage are simply the visible version of the same biology. ctDNA is the molecular version.
Tumors constantly shed DNA into the bloodstream, every tumor cell that dies or divides releases fragments of DNA into the blood. More tumor → more shedding → more ctDNA.
So ctDNA is proportional to total tumor mass. This is why papers emphasize ctDNA as a “real time measure of tumor burden” and why is used to direct and inform treatment effectiveness.
With an effective therapy tumor cells die (apoptosis, necrosis, reduced proliferation) → ctDNA shedding collapses, this drop happens days to weeks before a CT scan can show shrinkage .
Now, some are saying that the data that really matters is the one we will get in January 2027. I beg to differ and if the market keeps on showing (price) inefficiency, I will back up my truck and load (again). Why ??
Because ORR (tumor shrink ≥30% by RECIST) is just the imaging version of the same phenomenon!!
But RECIST shrinkage is slow: You need enough cell death to change tumor volume, you need enough time for the mass to physically shrink, you need a scan to measure it.
ctDNA doesn’t wait for any of that !!! It drops as soon as tumor cells stop shedding DNA.
But you don’t have to take my word for it: across colorectal cancer trials:
- Responders show ≥80–100% ctDNA decline
- Non-responders show <50% decline
- Some studies show no ORR at all when ctDNA decline is shallow
Objective responders universally had deep ctDNA clearance. Nonresponders did not.
It’s one of the cleanest biomarkers in oncology.
So, the correlation between ctDNA and ORR and tumor shrinkage is very strong because ctDNA is:
- directly proportional to tumor burden
- immediate (no imaging lag)
- global (all lesions)
- quantitative (exact numbers, not radiologist judgment)
- mechanistically linked to tumor biology (cell death → less shedding)
It’s not a surrogate. It’s the same signal, just measured earlier and more precisely.
From our data presented at AACR Annual Meeting 2026:
"Early clinical and biomarker responses were observed, including rapid and substantial reductions in circulating tumor DNA (ctDNA), with median declines of approximately 70% by week 2 across evaluable patients (N=19)"
I am sharing a paper (not sure it was shared before) that include 92 clinical studies and a short copy-and-paste of their results for those interested in deepening the understanding of the importance of our early and upcoming results in regard to ctDNA in our trial.
https://www.frontiersin.org/journals/genetics...01118/full
Results: Ninety-two clinical studies were included. These studies demonstrate that ctDNA is a reliable measure of tumor burden. Studies show the utility of ctDNA in assessing the adequacy of surgical tumor clearance and changes in ctDNA levels reflect response to systemic treatments. ctDNA can be used in the selection of targeted treatments. The reappearance or increase in ctDNA, as well as the emergence of new mutations, correlates with disease recurrence, progression, and resistance to therapy, with ctDNA measurement allowing more sensitive monitoring than currently used clinical tools.
Thank you for sharing the case of ctDNA readings for the patient, some comments below:
Why ctDNA data is so important: I am not pretending to contribute here something new (this all has been said before), this is just a reminder of the upcoming October data that we will likely receive containing ctDNA measurements following the context of the latest poster. You can call it a “bootstrap” if you like.
ctDNA is called a liquid biopsy because it lets doctor's “biopsy” a tumor using a simple blood (liquid) draw instead of cutting into tissue.
That’s the core idea — but here’s the deeper reasoning:
1. It captures tumor DNA directly from blood: Tumors constantly shed small fragments of DNA into the bloodstream. These fragments, circulating tumor DNA (ctDNA) carry the same mutations found in the tumor itself.
A blood sample containing ctDNA is therefore a biological snapshot of the tumor, just like a tissue biopsy.
2. It replaces or complements surgical tissue biopsy requiring: needles/endoscopy/surgery/anesthesia, the biopsy comes from blood (a liquid), not solid tissue.
3. It can be repeated frequently: tissue biopsies can’t be done every week. But ctDNA can be measured: weekly/biweekly/monthly, you can track tumor response in real time.
4. It detects microscopic disease, ctDNA can reveal: minimal residual disease (MRD), early relapse, treatment response, resistance mutations.
Often weeks or months before scans, which is why ctDNA decline is such a powerful early biomarker.
5. It reflects the whole tumor burden: a tissue biopsy samples one spot. ctDNA comes from all tumor sites, primary tumor + metastases because all shed DNA into blood.
This gives a more complete picture of tumor biology.
Now, because ctDNA is a direct, quantitative measurement of total tumor burden, it drops immediately when tumors die and rises immediately when tumors grow. ORR and RECIST shrinkage are simply the visible version of the same biology. ctDNA is the molecular version.
Tumors constantly shed DNA into the bloodstream, every tumor cell that dies or divides releases fragments of DNA into the blood. More tumor → more shedding → more ctDNA.
So ctDNA is proportional to total tumor mass. This is why papers emphasize ctDNA as a “real time measure of tumor burden” and why is used to direct and inform treatment effectiveness.
With an effective therapy tumor cells die (apoptosis, necrosis, reduced proliferation) → ctDNA shedding collapses, this drop happens days to weeks before a CT scan can show shrinkage .
Now, some are saying that the data that really matters is the one we will get in January 2027. I beg to differ and if the market keeps on showing (price) inefficiency, I will back up my truck and load (again). Why ??
Because ORR (tumor shrink ≥30% by RECIST) is just the imaging version of the same phenomenon!!
But RECIST shrinkage is slow: You need enough cell death to change tumor volume, you need enough time for the mass to physically shrink, you need a scan to measure it.
ctDNA doesn’t wait for any of that !!! It drops as soon as tumor cells stop shedding DNA.
But you don’t have to take my word for it: across colorectal cancer trials:
- Responders show ≥80–100% ctDNA decline
- Non-responders show <50% decline
- Some studies show no ORR at all when ctDNA decline is shallow
Objective responders universally had deep ctDNA clearance. Nonresponders did not.
It’s one of the cleanest biomarkers in oncology.
So, the correlation between ctDNA and ORR and tumor shrinkage is very strong because ctDNA is:
- directly proportional to tumor burden
- immediate (no imaging lag)
- global (all lesions)
- quantitative (exact numbers, not radiologist judgment)
- mechanistically linked to tumor biology (cell death → less shedding)
It’s not a surrogate. It’s the same signal, just measured earlier and more precisely.
From our data presented at AACR Annual Meeting 2026:
"Early clinical and biomarker responses were observed, including rapid and substantial reductions in circulating tumor DNA (ctDNA), with median declines of approximately 70% by week 2 across evaluable patients (N=19)"
I am sharing a paper (not sure it was shared before) that include 92 clinical studies and a short copy-and-paste of their results for those interested in deepening the understanding of the importance of our early and upcoming results in regard to ctDNA in our trial.
https://www.frontiersin.org/journals/genetics...01118/full
Results: Ninety-two clinical studies were included. These studies demonstrate that ctDNA is a reliable measure of tumor burden. Studies show the utility of ctDNA in assessing the adequacy of surgical tumor clearance and changes in ctDNA levels reflect response to systemic treatments. ctDNA can be used in the selection of targeted treatments. The reappearance or increase in ctDNA, as well as the emergence of new mutations, correlates with disease recurrence, progression, and resistance to therapy, with ctDNA measurement allowing more sensitive monitoring than currently used clinical tools.
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