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Liquid biopsies are changing how doctors learn about cancer. Instead of taking a tissue sample from a tumor, a liquid biopsy uses ablood draw to gather clues aboutɳ’shappening inside the body.Leading liquid biopsy expert, medical oncologist,ԻAssociate Director of Precision Oncology at theԹϸMeyer Cancer Center,Dr. MassimoCristofanilliexplainshow liquid biopsies work, why they matter, and where this fast-moving technology may go next.
For many years, a tissue biopsy has been the main way to diagnose cancer and guide treatment.Historically, these tissue samples have beenconsideredthe gold standard or the traditional way to assessthe histological diagnosis– or microscopic structure – ofcancer.Tissue samples can also be tested for biomarkers and genetic changes that help doctorsselectmore individualized treatments.
But,cancer canevolve.According toDr.Cristofanilli, tumors can be very heterogeneous, meaning their makeup can vary indifferent places,andmetastatic tumors indifferent partsof the body may not all look the same. Tumors can alsochange,adaptand evolveover time under the pressure of treatment.“That’s where liquid biopsy can be especially useful,becauseitis more of a real-time assessment of the diseasebiology,“Dr.Cristofanillisays.
Liquid biopsyblood testingusually refers to two related approaches. One looks for circulating tumor cells (CTCs)—rare cancer cells thathave escaped the tumor andentered the bloodstream.Thechallengeisthat circulating tumor cells are extremely rare in the peripheralbloodsotheyhavetobe separated out using specialized technology. One platform,䷡®, became the first FDA-approved test for counting these cellsapproximately 20 years ago.Using this CELLSEARCH®technology, cancer cells can be detected even if only one in a million cells is present in the body.Researchershavefound that in breast and prostate cancer, having five or moreof thesecirculating tumor cellsdetectedwas linked to more aggressive disease patterns.
The second approach looks for circulating tumor DNA (ctDNA), often measured throughwhat is called“cell-free DNA” tests.It is much more common for cell-free DNA to be circulating through the bloodstream.Dr.Cristofanilliexplainsthattypicallyonly a fraction of the cell-free DNAthat is detectedisactually tumorDNA, butthat thetechnology has improvedto be abletocapturevery smallamounts of tumor-derived DNAwith great sensitivity. This has opened new waysto track cancer changes over time,especially in advanced or metastaticdisease.
Liquid biopsy can also be faster and less invasive than a tissue biopsy.Tissue biopsies require physically accessing the tumor to send samples for genetic testing and pathology evaluation. Thistypically requires surgery or a minor procedure. In thecasesof smaller tumors or certain tumors that are harder to access in the body,obtainingtumor tissue can bemorechallenging and come withadditionalrisks. Even after a traditional tissue biopsy has been obtained,additionaltimedifferencespersist.“Areport from a cell-free DNAliquid biopsy testtakesanywherebetween five and seven days, while atissue biopsy withnext generation sequencing (NGS)or any molecular analysis takes at least two weeks,”says Dr.Cristofanilli.
A major advantage of liquid biopsy is thatthe resultsmay reflect cancer activity across multiple tumor sitesthroughout the bodyat once, for example breast cancer thatoriginates in thebreast and has spread to the liver. Dr.Cristofanillicallsthis “the most exciting aspect of molecular diagnostics.”
He adds, “You havetumorsshedding from multiple sitesso you can betterunderstand exactly the overall tumor burden and molecular representation of the disease.” This can be especially important when certain areas,like bone,aredifficultto biopsy.
Liquid biopsy is also starting to influence how doctors think about when to change treatment.Current research is underway todeterminewhen cell-freetumor DNA in the bloodhas shownsigns of treatment resistance, evenbefore scans showed visible growthof the cancer.This is referred toas “molecular progression,” meaning the cancer is showing molecular signs of change even if imaging still looks stable.
In a,liquid biopsy blood testswereutilizedfor early detection of a treatment-resistance mutation, followed by a switch to a new type of treatmentwhen the tumor DNA showed resistance. The researchdemonstratedthat the treatmentchangesignificantlyextendedthe period of tumor control compared to standard carein patients with advanced breast cancer.was conducted at multipleinternationalmedical centers, including at Թϸ andNewYork-Presbyterian.This wasone of the firstinstances showing thattreatmentchangesguided by liquid biopsy resultsbringsbetter outcomes for patients.
Dr.Cristofanillihighlightswhy this is such a major shift.“This is the first time, not only that we’rtreatingthe molecular progression, butin whichwe’ralsoable to determinethe specificdrug the cancer isdevelopingresistanceto,allowing us to bemore targeted in our approach to change therapy – in this case, only changing one drug when otherwise the practice had been to change the entire treatment.”While still a newer area of cancer research and treatment, theidea ofacting on molecular signals earlierin the course ofcancer carecould lead to new strategies for keeping cancer controlled longer and possibly delaying symptomsand side effects that patients experience.
In the future, Dr.Cristofanilliis especially excited aboutleveragingliquid biopsy forearly detection and making these tools more accessibleto more people. “The ability to detect very early onthe presence ofcancer can overcome many difficulties in terms of complianceԻaccess to screening,” heexplains. He alsoreinforcesthe need for tests that are easier and less expensive worldwide, noting that earliercancerdetection could havea huge impactinlow-resource settings.
As liquid biopsy technology continues to growand advance in sophisticationdzcapturingcirculating tumor cells and tumor DNA to newer approaches likedetectingDNA methylation signals—it may help doctors detect cancer sooner, personalize treatment more precisely, and monitor disease in ways that were not possible just a few years ago.
For an in-depth discussion on liquid biopsy and the technological advancements in this area, tune in to a recent episode of the ԹϸCancerCastPodcastwhereDr.Cristofanillisat down with hostDr. Manish Shahto delve into this topic.Listen on , , , or the .
