> ## Content Index > Fetch the complete content index at: https://www.eastrivernotes.com/llms.txt > Use this file to discover other available public pages before exploring further. # How does liquid biopsy work? - URL: https://www.eastrivernotes.com/liquid-biopsy/ - Published: 2026-08-28T22:27:43.000Z - Updated: 2026-08-28T22:28:03.000Z - Description: How cancers are detected by searching for tumor DNA fragments in blood samples. - Author: East River Notes - Tags: liquid biopsy, MRD, sequencing - Liquid biopsy is a blood test that detects signs of cancer. - Its main signal is circulating tumor DNA – fragments of DNA shed by dying tumor cells into the bloodstream. - This signal is rare, as DNA from normal cells vastly outnumbers that of tumor cells – it is like finding a needle in a haystack. - Recent advances in genomic sequencing make it possible to find the needle. - Liquid biopsy can be used for screening, monitoring after treatment, and choosing the treatment specific to that tumor’s mutations. - These tests are non-invasive, easier to administer, and – for known cancer mutations – able to detect its return months before it shows up on scans. The simple version As cancer cells grow and die, pieces of their DNA are released into the bloodstream – which can be detected with sequencing. ## How is cancer detected today? Cancer is traditionally detected either by taking a physical sample or by measuring markers that correlate with specific cancers. A conventional biopsy samples the tumor directly: a clinician retrieves tissue and a pathologist examines it. It is the standard of care, and has been proven to work. But it is invasive and is relatively difficult to do. And notably, it is local and momentary – while the disease by definition spreads and changes. Another method of detecting cancer is by testing for potential markers of one. Complete blood count (CBC) quantifies the blood cells by type and an abnormal reading could indicate a blood cancer. Peripheral smear examines cells under a microscope for unusual shapes. Blood chemistry and protein tests check for specific molecules that stressed organs or certain tumors release. Imaging scans (e.g. CT, MRI, PET) look for signs of abnormal growth once big enough to see. But these are indirect and not definitive. Counts and markers can move for benign reasons and stay quiet in many cancers. Scans can show clumps of overgrown cells, but cannot definitively identify the cancer. And none of these tools reads the tumor’s DNA itself. ## What is a liquid biopsy? A liquid biopsy looks for signs of cancer cells within a blood sample. Cancer cells undergo a rapid cycle of growth – and as tumors grow, many of their cells die and break down, spilling their internal contents, including their DNA, into the bloodstream. All cells shed DNA fragments into the blood as they die – **cell-free DNA (cfDNA)**. Tumor cells, unlike normal cells, release **circulating tumor DNA (ctDNA)**, and it can be identified because it carries the tumor’s mutations. That is what a liquid biopsy looks for. cfDNA and ctDNA have been known in the scientific community for a long time – since 1948 and 1989, respectively. But the technology to identify and quantify at scale with high precision has only recently been developed, with the prevalence of sequencing ([read the primer here](https://www.eastrivernotes.com/sequencing/)). Exhibit 1ctDNA in a blood sample A blood tube separates into layers; magnifying the plasma layer reveals a field of about 150 short gray DNA fragments from normal cells, among which only two red tumor-derived fragments sit. a tube of blood plasma blood cells plasma after filtering for DNA fragments tumor-derived fragments (ctDNA) cell-free DNA (cfDNA) – shed by normal cells Source: East River Notes, from company presentations, filings, and other publicly available information. Schematic; fragment counts illustrative. ## How does a test find tumor fragments in a blood sample? In advanced, widespread cancer, ctDNA fragments commonly make up 0.1–1.0% of total DNA fragments. In early-stage cancer, the number gets to 0.01% or lower – or one in ten thousand. Fortunately, recent advances in genomic sequencing enabled the technology to detect these. Below is a highly simplified explanation of the workflow: - **A)** Extract all the DNA fragments out from the blood sample - **B)** Only keep the parts of the DNA fragments that are of interest (i.e. only parts of the DNA where known mutations occur) - **C)** Sequence the enriched DNA fragments and look for specific mutations Note that in addition to looking for mutations, screening tests also read chemical marks on (and the sizes of) the DNA fragments. Exhibit 2From a blood draw to detecting a mutation Three panels: a spun blood tube yields cell-free DNA fragments; probes for known mutation sites capture only the regions of interest; sequencing reads the kept fragments letter by letter and flags the mutant base. A · EXTRACT B · ENRICH C · SEQUENCE plasma blood cells tumor fragments probes help filter to mutation sites ATGGACCT ATGGGCCT ATGGGCCT the mutation a tumor copy normal copies extract the cell-free DNAfragments from the plasma keep only the stretches whereknown cancer mutations occur sequence what remains andlook for the mutations A highly simplified targeted workflow. Real workflows also tag each fragment with a molecular barcode before sequencing, so sequencing errors can be told apart from true mutations.Source: East River Notes, from company presentations, filings, and other publicly available information. Schematic; simplified. If sequencing finds a trace of ctDNA above a defined threshold, the result is flagged as a potential sign of cancer. The tests can be assessed across two key metrics: **sensitivity** – of the people who truly have cancer, how many the test catches – and **specificity** – of the people who don’t, how many it correctly clears. Tune a test toward sensitivity and it catches more cancers but raises more false alarms; tune it toward specificity and a positive result is more trustworthy, but faint signals slip through. ## What are the different types of liquid biopsy? Liquid biopsy tests fall into three main categories: - **Therapy selection**: helps choose the optimal treatment plan after the patient is diagnosed - **Minimal residual disease (MRD)**: recurring tests to see if cancer has returned after the patient undergoes treatment - **Screening**: looking for potential signs of cancer before any diagnosis Exhibit 3Liquid biopsy tests throughout a patient’s journey A curve of tumor-DNA abundance over the disease course: a faint early rise where screening reads, a peak at advanced diagnosis where therapy selection reads, and a deep post-surgery trough where MRD testing reads. A dashed line marks roughly the smallest tumor a scan can see; MRD reads far below it, which is the source of its lead time over imaging. 1 in 100 1 in 10,000 1 in 1,000,000 tumor DNA, as a share of all cell-free DNA (log scale) ≈ the smallest tumora scan can see (\~1 cm) no diagnosis diagnosis treatment remission relapse relapse becomes visible on a scan screeningreads here therapy selectionreads here MRD reads here – months beforea scan can confirm the relapse Source: East River Notes, from company presentations, filings, and other publicly available information. Schematic; axes indicative, not patient data; the imaging threshold varies widely by tumor type and site. ## How is a liquid biopsy used to choose a therapy? Therapy selection is detecting and profiling cancer mutations, in order to help choose the best treatment plan. Many of these tests have been developed alongside the biopharma companies that develop cancer drugs. While the cancer drugs are being investigated, biopharma companies use these tests to profile cancer mutations and select patients for clinical trials. This way, the company can target the clinical trial towards the specific molecular subgroup. This is called a **companion diagnostic** – a test developed alongside a drug and approved to select patients for it. If the trial proved Drug A works in patients whose tumors carry mutation X, the same test that found those patients can be used to recommend Drug A to patients with mutation X. Generally, the more clinical trials and treatments a test has been validated with, the more useful it becomes in helping choose the right therapies. The test identifies specific mutations and suggests cancer drugs with evidence of benefit for that mutation. Liquid biopsy can also be run serially during the treatment and can observe the tumor shift during the process. A falling fragment count is an early sign the drug is working; a new resistance mutation can show it has stopped working – and suggest the next drug. Exhibit 4Illustrative example of lung cancer therapy selection A fictional lung-cancer patient's liquid biopsy report shows an EGFR mutation detected with ALK and KRAS negative; the result is matched against clinical trial evidence to a ranked list of therapies, and the physician selects the top-ranked drug. A patient is diagnosed with lung cancer LIQUID BIOPSY REPORT Patient · lung cancer EGFR mutation DETECTED ALK alteration negative KRAS mutation negative one driver mutation found matched against clinical trial evidence THERAPIES WITH EVIDENCE OF BENEFIT for EGFR-mutant lung cancer Drug A ★★★ Drug B ★★ Drug C ★ ★ strength of clinical evidence ✓ Physician selects Drug A A fictional patient: the test reads the tumor’s mutations from blood, the result is matched against clinical trial evidence, and the physician selects the therapy with the strongest evidence for that mutation.Source: East River Notes. Schematic; fictional patient, illustrative drugs. ## How does liquid biopsy detect cancer recurrence (MRD testing)? After a cancer treatment has concluded, it is often recommended that the patient get tested routinely to check whether the cancer has relapsed. Most of this has been done with imaging scans and simple blood tests measuring biomarkers. Recently, **minimal residual disease (MRD)** testing has been added alongside them – Medicare now covers ctDNA-based MRD testing in several common cancers. MRD uses sequencing to quantify the amount of ctDNA circulating in the blood sample. Because the most common MRD design is built from the patient’s own tumor and knows which mutations to look for, it can detect signs of cancer with a high degree of accuracy and precision. In published studies, ctDNA-based MRD tests have flagged recurrence months before imaging – roughly half a year ahead in colorectal cohorts and closer to a year in breast, with shorter leads in lung and pancreatic cancer. In certain ultrasensitive assays, MRD testing can flag a relapse a year or more before it is visible on a scan. The ability to detect signs of cancer returning months earlier changes how the disease can be managed. Catching a recurrence early opens up options that a scan-visible relapse may not: closer monitoring, earlier imaging, and in some cases, local treatment while the disease is still small. Notably, a consistently negative MRD test provides reassurance that the cancer is less likely to return, and has allowed some patients to safely skip unnecessary chemotherapy, while still continuing to monitor. MRD tests are also much easier to administer than the alternatives. A blood draw takes minutes, needs no preparation, and carries virtually no risk of complications – and unlike frequent CT or PET scans, it carries no radiation, so it can be repeated as often as needed. Repeated draws build a longitudinal picture of a disease that is dynamic by nature: a physical biopsy captures one spot at one moment, while MRD testing captures fragments from the body as a whole. The low friction also makes patients more likely to keep up with testing, and samples can be drawn locally and shipped for processing, sparing clinical capacity for other patients. Cancer care historically looked something like this: treat, then scan at intervals, then react to what the scan shows. Rather than waiting months for a cancer to potentially show up on a scan, MRD can catch relapses early, which provides more time and opportunities to manage the disease. And because blood tests can be done more regularly, doctors have more data points and information during surveillance. Exhibit 5Illustrative paths of cancer recurrence, with and without MRD One patient finishes treatment and is watched two ways. On the top lane, without MRD, the cancer quietly returns and stays invisible until a scan finally detects it, leaving fewer and more aggressive options. On the bottom lane, routine blood draws flag the recurrence months earlier, opening a shaded window of opportunity for closer monitoring and earlier intervention, with potentially broader options. treatment ends, surveillance begins WITHOUT MRD □ scan cancer quietly returns no symptoms – patient feels well imaging finally detects the recurrence disease more advanced; fewer, more aggressive treatment options WITH MRD cancer quietly returns the next blood draw: MRD becomes positive closer monitoring · earlier intervention more time to treat; potentially broader treatment options the window of opportunity recurrence detected months before a scan • routine blood draw Source: East River Notes. Schematic; fictional patient, timing illustrative. ## How is liquid biopsy used for screening? ctDNA fragment detection can be used to find potential signs of cancer before patients are diagnosed. There are two general types of ctDNA screening: single-cancer and **multi-cancer early detection (MCED)**. Single-cancer screenings look for specific genomic markers associated with a single organ’s tumors. These are used for people who need regular screening but want a simpler option: a blood draw is easier to administer, with no preparation and less friction for patients. An example is colorectal screening. In 2024, the FDA approved the first blood test as a primary screening option for colorectal cancer in average-risk adults. The appeal is that individuals are more likely to come in for a simple blood draw, or as a part of annual physicals, than to go through colonoscopy or stool sampling. Roughly two in five age-eligible U.S. adults (ages 45–75) are not up to date on any colorectal screening – a gap the blood tests aim to close. Another type of screening is MCED (multi-cancer early detection). These tests cast a wide net and screen for dozens of cancers at once. They are designed to flag potential signs of cancer in healthy patients that are not actively being monitored, especially for the cancers with no routine screening options (e.g. pancreatic, ovarian, or esophageal cancers). Screening tests also look for a different kind of fingerprint. Rather than hunting only for specific mutations, most read chemical marks on the DNA (**methylation**) and the sizes of the fragments – patterns that distinguish tumor DNA from normal DNA. The main benefit of these tests is accessibility: it is used as a preliminary screening, and those who may need further diagnosis get escalated. ctDNA screening tests are designed to complement – not replace – standard screenings like mammograms and colonoscopies; they are positioned as low-friction, first-pass tools. Because ctDNA increases as cancer cells grow, screening tests tend to be less sensitive while cancers are in their early stages. The exception is MRD, where the test is built from the patient’s own tumor and already knows what to look for. A screening test has no such prior knowledge. But as a triage tool, the ctDNA screening tools can work well. The point is to increase access and catch more people earlier in the cancer journey – an easy test that sorts out who needs a scan or a biopsy to confirm. Exhibit 6Illustrative journey from screening to diagnosis Forty illustrative people take a simple blood draw. Thirty-seven test negative and return to routine care; three are flagged and enter the diagnostic workup of imaging, colonoscopy, biopsy, and specialist evaluation, where one cancer is confirmed and found early and two clear as false alarms. 40 people without a cancer diagnosis (illustrative) a simple blood draw (ctDNA screening) 37 of 40 test negative – back to routine care 3 of 40 flagged – positive / suspicious DIAGNOSTIC WORKUP imaging · colonoscopy · biopsy · specialist 1 confirmed – cancer found early 2 cleared on follow-up – false alarms ctDNA screening is a low-friction triage tool – not a replacement for diagnostic testing. In practice far fewer are flagged than shown here, and roughly one cancer is found per 150–200 people screened.Source: East River Notes. Schematic; counts simplified for readability. ## How is liquid biopsy changing cancer care? Liquid biopsy is already becoming part of cancer care. Therapy selection has become standard practice in advanced lung cancer and a growing list of others. MRD is now reimbursed by Medicare in several common cancers and increasingly adopted. Screening is FDA-approved for one cancer – two colorectal blood tests, in 2024 and 2026 – and the first multi-cancer test is under FDA review. Easily accessible and familiar blood draws allow screening to be done at much larger scale – and can reach populations that may be far away from major academic centers or hospitals. Even though the tests may miss some cancers in early stages, screening tools flag people for a closer look before symptoms or a scan would. ## Takeaways - A liquid biopsy identifies and counts fragments of tumor DNA that are shed into the blood. - Advances in genomic sequencing and vastly reduced costs have enabled these technologies. - ctDNA tests help guide patients through cancer therapies, run routine surveillance for potential relapses, and screen for warning signs before diagnosis. - Liquid biopsy is established for therapy selection and is being adopted for surveillance and screening as the evidence matures. One line to remember Liquid biopsy turns cancer detection from an occasional, invasive look at one spot into a repeatable, quick test that samples the whole body. General, educational, and informational research only, not tailored to your situation. Nothing here constitutes investment, legal, medical, or other professional advice; an offer to sell or a solicitation of an offer to buy any security; promotional or marketing material; or a recommendation. The author may hold positions in the securities or sectors discussed. Do your own research and consult a licensed professional. Full disclosures at [www.eastrivernotes.com/disclosures](https://www.eastrivernotes.com/disclosures/). #### Notes The mechanism, test performance, and approval history described here are synthesized from company presentations, filings, published clinical-trial results, peer-reviewed literature, and other publicly available information. Quantitative figures in the text – ctDNA fractions and detection floors, sensitivity and specificity ranges, lead times over imaging, and the sizes at which scans first detect tumors – are rounded and estimated, representative of published cohorts and the current market rather than values precise to any single test, tumor type, or patient. Exhibits are illustrative and schematic, not to scale. Some technical terms are deliberately simplified for a general reader without changing their underlying meaning. This primer favors durable concepts over point-in-time statistics. ##### On this page 1. [How is cancer detected today?](#s0) 2. [What is a liquid biopsy?](#s1) 3. [How does a test find tumor fragments in a blood sample?](#s3) 4. [What are the different types of liquid biopsy?](#types) 5. [How is a liquid biopsy used to choose a therapy?](#s4) 6. [How does liquid biopsy detect cancer recurrence (MRD testing)?](#s5) 7. [How is liquid biopsy used for screening?](#s6) 8. [How is liquid biopsy changing cancer care?](#s7) 9. [Takeaways](#takeaways) ##### Key terms **ctDNA** – DNA fragments of cancer cells in plasma **Liquid biopsy** – test that detects signs of cancer in blood samples, usually with genomic sequencing **Therapy selection** – test that detects specific mutations to help inform optimal cancer treatment plan **MRD testing** – test for minimal residual disease: checks whether cancer has returned after treatment has concluded **Sensitivity** – a test's ability to catch positive cases **Specificity** – a test's ability to correctly identify those who do not have a condition ##### About East River Notes publishes independent research and deep dives on businesses, systems, and trends in healthcare.