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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 a听蝉颈尘辫濒别听blood draw to gather clues about听飞丑补迟鈥檚听happening inside the body.听Leading liquid biopsy expert, medical oncologist,听补苍诲听Associate Director of Precision Oncology at the听AV研究所听Meyer Cancer Center,听Dr. Massimo听Cristofanilli听explains听how liquid biopsies work, why they matter, and where this fast-moving technology may go next.听
For many years, a tissue biopsy has been the main way to diagnose cancer and guide treatment.听Historically, these tissue samples have been听considered听the gold standard or the traditional way to assess听the histological diagnosis听鈥 or microscopic structure 鈥 of听cancer.听Tissue samples can also be tested for biomarkers and genetic changes that help doctors听select听more individualized treatments.听
But,听cancer can听evolve.听According to听Dr.听Cristofanilli, tumors can be very heterogeneous, meaning their makeup can vary in听different places,听and听metastatic tumors in听different parts听of the body may not all look the same. Tumors can also听change,听adapt听and evolve听over time under the pressure of treatment.听鈥That鈥檚 where liquid biopsy can be especially useful,听because听it听is more of a real-time assessment of the disease听biology,鈥听Dr.听Cristofanilli听says.听
Liquid biopsy听blood testing听usually refers to two related approaches. One looks for circulating tumor cells (CTCs)鈥攔are cancer cells that听have escaped the tumor and听entered the bloodstream.听The听challenge听is听that circulating tumor cells are extremely rare in the peripheral听blood听so听they听have听to听be separated out using specialized technology. One platform,听颁贰尝尝厂贰础搁颁贬庐, became the first FDA-approved test for counting these cells听approximately 20 years ago.听Using this CELLSEARCH庐听technology, cancer cells can be detected even if only one in a million cells is present in the body.听Researchers听have听found that in breast and prostate cancer, having five or more听of these听circulating tumor cells听detected听was linked to more aggressive disease patterns.听
The second approach looks for circulating tumor DNA (ctDNA), often measured through听what is called听鈥渃ell-free DNA鈥 tests.听It is much more common for cell-free DNA to be circulating through the bloodstream.听Dr.听Cristofanilli听explains听that听typically听only a fraction of the cell-free DNA听that is detected听is听actually tumor听DNA, but听that the听technology has improved听to be able听to听capture听very small听amounts of tumor-derived DNA听with great sensitivity. This has opened new ways听to track cancer changes over time,听especially in advanced or metastatic听disease.听
Liquid biopsy can also be faster and less invasive than a tissue biopsy.听Tissue biopsies require physically accessing the tumor to send samples for genetic testing and pathology evaluation. This听typically requires surgery or a minor procedure. In the听cases听of smaller tumors or certain tumors that are harder to access in the body,听obtaining听tumor tissue can be听more听challenging and come with听additional听risks. Even after a traditional tissue biopsy has been obtained,听additional听time听differences听persist.听鈥A听report from a cell-free DNA听liquid biopsy test听takes听anywhere听between five and seven days, while a听tissue biopsy with听next generation sequencing (NGS)听or any molecular analysis takes at least two weeks,鈥听says Dr.听Cristofanilli.听
A major advantage of liquid biopsy is that听the results听may reflect cancer activity across multiple tumor sites听throughout the body听at once, for example breast cancer that听originates in the听breast and has spread to the liver. Dr.听Cristofanilli听calls听this 鈥渢he most exciting aspect of molecular diagnostics.鈥澨听
He adds, 鈥You have听tumors听shedding from multiple sites听so you can better听understand exactly the overall tumor burden and molecular representation of the disease.鈥 This can be especially important when certain areas,听like bone,听are听difficult听to biopsy.听
Liquid biopsy is also starting to influence how doctors think about when to change treatment.听Current research is underway to听determine听when cell-free听tumor DNA in the blood听has shown听signs of treatment resistance, even听before scans showed visible growth听of the cancer.听This is referred to听as 鈥渕olecular progression,鈥 meaning the cancer is showing molecular signs of change even if imaging still looks stable.听听
In a听,听liquid biopsy blood tests听were听utilized听for early detection of a treatment-resistance mutation, followed by a switch to a new type of treatment听when the tumor DNA showed resistance. The research听demonstrated听that the treatment听change听significantly听extended听the period of tumor control compared to standard care听in patients with advanced breast cancer.听听was conducted at multiple听international听medical centers, including at AV研究所 and听NewYork-Presbyterian.听This was听one of the first听instances showing that听treatment听changes听guided by liquid biopsy results听brings听better outcomes for patients.听
Dr.听Cristofanilli听highlights听why this is such a major shift.听鈥淭his is the first time, not only that we鈥檙别听treating听the molecular progression, but听in which听we鈥檙别听also听able to determine听the specific听drug the cancer is听developing听resistance听to,听allowing us to be听more targeted in our approach to change therapy 鈥 in this case, only changing one drug when otherwise the practice had been to change the entire treatment.鈥听While still a newer area of cancer research and treatment, the听idea of听acting on molecular signals earlier听in the course of听cancer care听could lead to new strategies for keeping cancer controlled longer and possibly delaying symptoms听and side effects that patients experience.听
In the future, Dr.听Cristofanilli听is especially excited about听leveraging听liquid biopsy for听early detection and making these tools more accessible听to more people. 鈥淭he ability to detect very early on听the presence of听cancer can overcome many difficulties in terms of compliance听补苍诲听access to screening,鈥 he听explains. He also听reinforces听the need for tests that are easier and less expensive worldwide, noting that earlier听cancer听detection could have听a huge impact听in听low-resource settings.听
As liquid biopsy technology continues to grow听and advance in sophistication鈥撵谤辞尘听capturing听circulating tumor cells and tumor DNA to newer approaches like听detecting听DNA methylation signals鈥攊t may help doctors detect cancer sooner, personalize treatment more precisely, and monitor disease in ways that were not possible just a few years ago.听
For an in-depth discussion on liquid biopsy and the technological advancements in this area, tune in to a recent episode of the AV研究所听CancerCast听Podcast听where听Dr.听Cristofanilli听sat down with host听Dr. Manish Shah听to delve into this topic.听Listen on听鈥,鈥,听鈥, or the听鈥.听
