Cancer that remains after treatment at a level too low to see on a scan, detected by sequencing tumor DNA fragments shed into the blood (ctDNA).
After surgery or therapy, a patient can look cancer-free on imaging yet still harbor a small number of tumor cells. Molecular residual disease (MRD) is that hidden remnant, detected not by a scan but by looking for circulating tumor DNA (ctDNA) — fragments of tumor DNA shed into the bloodstream — using sensitive sequencing.
The most accurate MRD tests are tumor-informed: the lab first sequences the patient's tumor to build a personalized panel of that tumor's specific mutations, then watches the blood for those exact mutations over time. This is the same starting point as a personalized neoantigen vaccine — sequence the tumor, find its private mutations — which is why MRD and neoantigen work are close cousins. A positive ctDNA result is a strong early signal that cancer will recur, often months before a scan shows anything.
For the vaccine field, MRD matters as a tool, not a competitor. It is a natural way to enroll the right patients into adjuvant vaccine trials (those with detectable residual disease, at highest risk) and a fast early readout of whether a therapy is working — clearing ctDNA — long before survival curves mature. ASCO 2026's CIRCULATE trial, which used ctDNA to decide who received chemotherapy, is an example of the paradigm, and a reminder that the approach is still being validated.
MRD is cancer that persists after treatment at a level too low to detect on imaging. It is found by testing the blood for circulating tumor DNA (ctDNA) — tumor DNA fragments shed into the bloodstream — using sensitive sequencing. A positive result often predicts recurrence months before a scan would.
Both start from the same step: sequencing a patient's tumor to identify its specific mutations. Tumor-informed MRD tests track those mutations in the blood; personalized neoantigen vaccines turn them into targets. In trials, MRD is increasingly used to select high-risk patients for adjuvant vaccines and as an early signal of whether the therapy is clearing residual disease.
A tumor-informed (bespoke) MRD test first sequences the patient's tumor to build a personalized panel of that tumor's mutations, giving very high specificity. A tumor-naïve test looks for a fixed, predefined set of cancer markers without sequencing the tumor first — faster to deploy but generally less sensitive for very low disease levels.