Breakthroughs in the Blood: Leveraging Liquid Biopsy to Improve Cancer Care

In their incessant pursuit of growth, tumors cultivate chaotic conditions characterized by high cellular turnover—and dead and dying cancer cells that leak their core components into circulation. Finding these faint traces of cancer in the bloodstream was once an insurmountable technical challenge, but liquid biopsy breakthroughs presented at the AACR Annual Meeting 2025, held April 25-30, revealed how far these technologies have come and their immense clinical potential. In particular, circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) can provide crucial insights about cancer’s identity and help guide decisions about care.

Intercepting (Nearly) Invisible Cancer: ctDNA-guided Immunotherapy

A phase II study presented during the “Advances in Immunotherapy” Clinical Trials Plenary Session by Yelena Y. Janjigian, MD, of Memorial Sloan Kettering Cancer Center (MSKCC), captured one of the most striking uses of liquid biopsy to date: intercepting cancer at the first signs of relapse.

Patients with early-stage, DNA mismatch repair-deficient (dMMR) solid cancers underwent surgery and were then screened for residual disease at six to 10 weeks. Those with detectable ctDNA, a sign of lingering cancer, were treated with pembrolizumab (Keytruda), a PD-1 immune checkpoint inhibitor. The results were stunning: 86.4% (11/13) of ctDNA-positive patients cleared their disease and remained recurrence-free at the two-year mark, compared to 66.7% (4/6) of ctDNA-positive patients who could not receive pembrolizumab and 98% (149/152) of ctDNA-negative patients.

“The study suggests that ctDNA-guided treatment strategies may help prevent relapse in patients whose tumors would otherwise recur … and can effectively eliminate residual disease before macroscopic recurrence occurs,” Janjigian said in a press release.

“Our findings lay the groundwork for future trials to validate ctDNA as a predictive biomarker and ultimately improve outcomes for patients with curable malignancies, ensuring that high-risk patients receive timely intervention while avoiding overtreatment in those who are unlikely to benefit,” Janjigian added.

By catching the molecular signs of relapse months before clinical evidence emerged, doctors could act swiftly to prevent cancer from roaring back. As Janjigian emphasized, ctDNA isn’t just a passive predictor anymore, it’s becoming a dynamic compass, steering timely interventions and potentially saving lives.

Early Warning: Catching Cancer’s Comeback Months Ahead

The sooner doctors can catch signs of possible relapse the better—and Emma Titmuss, MSc, and Jonathan Loree, MD, MS, both of BC Cancer in Vancouver, showed what current technologies can achieve during the “Liquid Biopsy: Circulating Nucleic Acids” Minisymposium and a press conference.

In the VICTORI study, liquid biopsy detected all post-resection clinical recurrences in patients with colorectal cancer before imaging did, often well in advance. The ultrasensitive NeXT Personal assay, guided by a personalized, tumor tissue-derived panel of up to 1,800 somatic variants for each patient, was able to detect ctDNA as low as two parts per million, a staggering level of sensitivity. As a result, half of cancer recurrences were detected at least six months prior to imaging, and in some cases ctDNA signaled relapse more than a year before a tumor showed up on scans.

“The results from our study help to clarify the ideal timepoint for ctDNA testing following a surgical procedure,” Titmuss said. Though ctDNA was detectable at two weeks post-resection, the team noted that the stress of surgery may also spike cfDNA levels and partially dilute the ctDNA signal, making it less reliable so soon after resection. This led them to suggest that measuring cfDNA at four weeks might be more appropriate and provide more accurate and actionable intel.

The clinical implications are profound. Earlier detection means earlier intervention, and offers a valuable window where treatments might be most effective. For patients who stay ctDNA-negative, it provides peace of mind without overexposure to radiation from frequent scans. In that sense, liquid biopsy is evolving into a safer, more sensitive early warning system, a kind of “check engine” light for cancer.

Beyond Mutations: Unlocking the Power of Fragmentomics

Tracking tumors’ mutational signatures via ctDNA, as powerful as it can be, may not always tell the whole story. In the aforementioned Minisymposium, Valsamo Anagnostou, MD, PhD, of Johns Hopkins Medicine, presented a peek at a possible future approach: going beyond looking for mutations, and instead analyzing the entire “fragmentome” of cfDNA.

Her team’s research showed that fragmentomic patterns—the size, structure, and distribution of cfDNA fragments in the blood—was connected to outcomes in lung cancer patients treated with immunotherapy. Crucially, this method requires only tiny amounts of blood and doesn’t depend on tracking specific mutations, making it potentially applicable across many cancer types.

As Anagnostou framed it, “This is truly exciting in terms of the clinical impact, because we’re starting with really low quantities of cell-free DNA, down to one nanogram in a few milliliters of plasma, so this is a very clinically feasible approach.”

Fragmentomics could offer a broader view of cancer’s behavior, especially with respect to cancer cell turnover and genome stability, capturing disease dynamics that can complement mutation-based monitoring. It’s a new dimension of blood-based cancer surveillance, hinting at an era where one simple draw could provide doctors with important insights to inform their decision-making.

The Road Ahead: From Dream to Daily Practice

Taken together, this small sample of studies at the AACR Annual Meeting 2025 showed that liquid biopsy is crossing a threshold for cancer care. Blood is becoming one of oncology’s most powerful diagnostic and monitoring mediums. The field still faces challenges, especially developing approaches that can be applied to cover patients with a wider range of cancers, but the direction of travel is unmistakable.