ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment

Short pieces of DNA floating in the blood, shed by dying cells all over the body. Most is from normal cells; the small tumour-derived fraction (ctDNA) is what liquid biopsies fish out.

Circulating tumour DNA (ctDNA) consists of fragments of DNA shed by tumour cells into the blood, detectable with sensitive sequencing.

A blood test that reads fragments of DNA shed by the tumour, so you can genotype or monitor cancer without a needle in the tumour.

Klaus Pantel is a pioneer of circulating tumour cell research and the liquid biopsy field.

Circulating tumour DNA (ctDNA) consists of fragments of DNA shed by tumour cells into the blood, detectable with sensitive sequencing.

A blood test that reads fragments of DNA shed by the tumour, so you can genotype or monitor cancer without a needle in the tumour.

Showed that whole-exome sequencing of blood can track how a cancer evolves, and co-founded Inivata.

A ctDNA pioneer whose early work showed blood could track breast cancer better than protein markers or imaging.

Co-developed CancerSEEK, the blood test that showed multi-cancer early detection is possible, and ran the first prospective screening study of it.

Used ctDNA to show how colorectal cancers evolve resistance to EGFR antibodies and how that resistance can fade.

Led DYNAMIC, the first randomised trial to show ctDNA can safely guide who needs chemotherapy after colon cancer surgery.

A tumour is a population that evolves by natural selection. Treatment kills the sensitive cells and selects the rest, which is why resistance is the rule; measuring the surviving population (MRD) and adapting therapy is the counter-strategy.

The lung cancer gene test that became the first blood-based companion diagnostic the FDA ever approved.

A blood test that reads a tumour's mutations without a tissue biopsy and is the FDA-approved gateway to several targeted drugs.

The FDA-approved tissue (324 genes) and blood genomic tests that serve as companion diagnostics for dozens of drugs.

The test that decides whether a specific drug is right for you, approved together with the drug.

Creator of Herceptin, Avastin, and Rituxan, and owner of Foundation Medicine; the company that defined antibody oncology.

Liquid biopsy leader: Guardant360 for genotyping, Reveal for MRD, Shield for screening.

Maker of the FDA-approved FoundationOne CDx genomic test used across dozens of drug labels.

Erlotinib was one of the first EGFR pills for lung cancer; it was approved before anyone knew EGFR mutations predicted who would respond, then redefined by them.

Osimertinib (Tagrisso) is the standard pill for EGFR-mutant lung cancer, now also given after surgery and with chemotherapy or after chemoradiation.

Signatera is Natera's tumour-informed blood test that tracks 16 mutations from each patient's own tumour to detect residual or returning cancer after surgery. Medicare covers it in colorectal, breast, bladder, lung and ovarian cancer and for immunotherapy monitoring, and in 2026 it selected the bladder cancer patients for the first approval based on circulating tumour DNA.

Natera makes Signatera, the dominant tumour-informed MRD test.

An ultra-sensitive blood test after surgery that detects leftover cancer months before a scan would.

Cancer still present after treatment but too small to see on scans, detected by blood or marrow tests.

A tumour-informed blood test is built for one patient: the tumour is sequenced first and the test then hunts for that patient's own mutations in blood. A tumour-naive test uses the same fixed panel, often of methylation marks, for everyone, so it needs no tumour sample and returns faster.

A blood test for leftover cancer after surgery that needs no tumour sample, so results come faster than tumour-informed tests.

NeoGenomics' personalised blood test for tiny amounts of leftover cancer, tracking up to 48 mutations from the patient's own tumour.

In 1,039 Japanese patients with resected colorectal cancer, a positive Signatera test at week 4 carried a tenfold higher recurrence risk, and only ctDNA-positive patients appeared to benefit from adjuvant chemotherapy.

Japan's national programme tests whether a blood test after surgery should decide who gets chemotherapy, and whether treating a positive test early helps.

Medicare's way of paying for a promising but uncertain test or treatment only for patients enrolled in a registry or study, used for PET scans in cancer from 2006 and now the frame for how Medicare covers gene panels and cell therapies.

Showed that a blood test can safely halve the number of colon cancer patients given chemotherapy after surgery.

Giving chemotherapy only to patients with tumour DNA in their blood after surgery cut chemotherapy use from 28% to 15% with no loss in recurrence-free survival at two years.

Japan's national programme tests whether a blood test after surgery should decide who gets chemotherapy, and whether treating a positive test early helps.

A UK study following 1,000 people after bowel cancer surgery with repeated blood tests for tumour DNA, to see how well a positive predicts the cancer coming back and whether the result can guide chemotherapy.

Natera's US study in which 1,788 people with bowel cancer had Signatera blood tests after surgery and their doctors could act on the result; it records what changed and what happened, but does not randomise anyone.

A lung cancer trial that planned to test whether adding the immunotherapy durvalumab to chemotherapy after surgery helps people whose blood shows leftover tumour DNA; the registry lists it as complete with 89 participants.

A lung cancer trial that planned to start durvalumab the moment a surveillance blood test found tumour DNA, before any scan showed relapse; the registry lists it as complete with 30 participants.

A ctDNA MRD blood test after surgery decides who gets more treatment and who is spared it.

Giving less treatment to patients who are doing well and more to those who are not, using a marker such as scan response, ctDNA or MRD to decide. The aim is to cure the same number of people with less harm.

An oral chemotherapy pill for bowel cancer that has stopped responding to everything else; with bevacizumab it extends life by about three months.

The cancer where screening works best and where immunotherapy can make some tumours disappear entirely, yet most metastatic disease still depends on chemotherapy.

The first trial to use a blood test for leftover cancer to decide who gets immunotherapy, and it worked.

Patients whose blood turned positive for tumour DNA after cystectomy lived longer with atezolizumab than placebo; patients who stayed ctDNA-negative did well without any treatment. It is the first ctDNA-guided adjuvant trial to improve survival.

A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery.

Signatera is Natera's tumour-informed blood test that tracks 16 mutations from each patient's own tumour to detect residual or returning cancer after surgery. Medicare covers it in colorectal, breast, bladder, lung and ovarian cancer and for immunotherapy monitoring, and in 2026 it selected the bladder cancer patients for the first approval based on circulating tumour DNA.

Led EV-302, NIAGARA and IMvigor011, the trials that transformed bladder cancer from chemotherapy-only to ADC, immunotherapy and ctDNA-guided care.

Bladder cancer went from 40 years of cisplatin to an ADC-immunotherapy combination that nearly doubled survival, and in 2026 the first blood-test-guided drug approval.

The test that decides whether a specific drug is right for you, approved together with the drug.

A single blood test intended to screen for dozens of cancers at once, including ones with no screening today.

A blood test screening for more than 50 cancers at once, before the FDA in September 2026.

The first FDA-approved blood test for colorectal cancer screening (2024), now optionally reporting other cancers too.

GRAIL developed Galleri, the multi-cancer blood test awaiting an FDA decision after a September 2026 advisory committee.

Liquid biopsy leader: Guardant360 for genotyping, Reveal for MRD, Shield for screening.

PATHFINDER 2 is the US real-world study of the Galleri test that forms the core of its FDA submission.

The largest cancer screening trial ever run, testing whether a multi-cancer blood test reduces late-stage diagnoses.

The study behind the first approved blood test for bowel cancer screening: it found 83% of cancers but only 13% of advanced polyps.

In 6,621 adults over 50, the Galleri test flagged a cancer signal in 1.4%, of whom 38% turned out to have cancer; diagnostic work-up took about two months for true positives and over five months for false positives.

The NHS-Galleri design paper is the protocol for a 140,000-person randomised trial in England testing whether three annual Galleri blood tests reduce late-stage (III-IV) cancer diagnoses, the first MCED trial powered for a stage-shift endpoint.

Blood tests that read chemical marks on fragments of DNA shed by tumours; the marks tell cancer DNA from normal DNA and hint at where the cancer is.

Stage shift means finding more cancers early and fewer late; it is the measurable goal of screening.

Positive predictive value (PPV) is the chance that a positive test result is actually right: true positives divided by all positives. Because it falls as a disease becomes rarer, even a specific screening test gives mostly false alarms when prevalence is low, which is why PPV decides whether a multi-cancer blood test is useful.

Led PATHFINDER, the first prospective study of a multi-cancer blood test in practice, and the PROSPECT rectal cancer trial.

Epidemiologist who showed HPV vaccination has nearly eliminated cervical cancer in vaccinated English women and leads NHS-Galleri.

The US government's first randomised study of multi-cancer blood tests: 24,000 people are being assigned to a blood test or usual care to work out how a much larger trial should be run.

The US national trial that uses a blood test for leftover tumour DNA to decide who gets less chemotherapy and who gets more after stage III colon cancer surgery, with both questions randomised.

A UK study following 1,000 people after bowel cancer surgery with repeated blood tests for tumour DNA, to see how well a positive predicts the cancer coming back and whether the result can guide chemotherapy.

Japan's national programme tests whether a blood test after surgery should decide who gets chemotherapy, and whether treating a positive test early helps.

The NCI is the US government's cancer research agency, spending ~$7B a year and running the Cancer Centers Program, TCGA, and Rosenberg's cell therapy lab.

The US cooperative group formed from the radiation, gynaecologic, and breast trial groups; it co-led OlympiA, the trial that put a PARP inhibitor after surgery for BRCA carriers.

Use a blood test after surgery to decide who gets chemotherapy: spare the negatives, and find something that actually works for the positives.

If a blood test reliably shows whether cancer will come back after surgery, trials could use it instead of waiting years for relapse. Regulators have a process to bless such a test; oncology should use it.

A surrogate endpoint only deserves trust if trials have shown that moving it moves the outcome that matters, in that disease and for that kind of drug; some stand-ins have passed that test, several have not, and the record differs endpoint by endpoint.

Blood tests that read chemical marks on fragments of DNA shed by tumours; the marks tell cancer DNA from normal DNA and hint at where the cancer is.

Fragmentomics reads the sizes and positions of DNA fragments in blood, not the mutations. Cancer cells die messily and leave a recognisable fragmentation pattern.

Reading chemical tags on DNA that reveal a cell's identity, used to classify brain tumours and to detect cancer in blood.

Instead of testing blood every three months, sampling constantly, so a relapse is caught the week it starts.

Fragmentomics company whose FirstLook Lung blood test aims to raise lung-cancer screening uptake; first randomised clinical-utility data in 2026.

Freenome makes SimpleScreen CRC, the second FDA-approved blood test for colorectal cancer screening (July 2026), commercialised by Abbott.

A blood test for leftover cancer after surgery that needs no tumour sample, so results come faster than tumour-informed tests.

As we age, blood stem cells with cancer-like mutations quietly expand in most people. These clones raise leukaemia and heart disease risk, are accelerated by chemotherapy, and confuse blood tests for cancer DNA.

The speed at which a molecular marker falls during treatment predicts outcome better than a single level: BCR-ABL halving time in chronic myeloid leukaemia and circulating tumour DNA slopes in solid tumours are now used to judge response within weeks.

Current blood tests for leftover cancer track a few dozen mutations and miss low-level disease. Whole-genome and error-corrected methods integrate signal across thousands of tumour-specific sites plus methylation and fragment features, reaching detection near one part per million in research settings; cost, turnaround and reproducibility are the barriers.

Tumour DNA in blood can be told apart by chemical marks as well as mutations. Marks are more numerous and cheaper to read, so they could track more sub-populations for less money.

Medicare's way of paying for a promising but uncertain test or treatment only for patients enrolled in a registry or study, used for PET scans in cancer from 2006 and now the frame for how Medicare covers gene panels and cell therapies.

Most cancer tests in the US, including Galleri, Signatera and Oncotype DX, are 'lab-developed tests' overseen through lab standards rather than FDA approval; the FDA's 2024 attempt to change that was struck down in court in 2025.

Leftover-cancer blood tests are being sold faster than evidence that acting on them helps. Paying for them only when the result is recorded would generate the missing evidence.

Dozens of companies sell blood tests for tumour DNA and they report different results on the same sample. Government-issued reference samples with known amounts of tumour DNA would expose the differences.

Different companies' leftover-cancer blood tests disagree, and there is no shared yardstick. Public reference samples would let anyone check which test actually works.

A positive blood test with no known tumour is frightening and hard to manage. A standard imaging cascade with a time limit, and a registry of what was found, would make these tests usable.

After a 'successful' treatment, cells can sleep for years then relapse. We can barely detect them and cannot target them.