The American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego reflected how precision oncology goals are shifting. The questions have evolved from whether we can detect cancer signals to whether we can measure them well enough to act on them.
Across plenary sessions, oral presentations, and poster discussions, a consistent theme emerged: the capacity to detect circulating tumor DNA (ctDNA) and other blood-based biomarkers has advanced considerably, yet the constraints on clinical translation are increasingly analytical rather than biological. Reproducibility and precise quantification are now recognized as central challenges, particularly as liquid biopsy applications move from research settings into clinical trials.
Here, I report on the most compelling new liquid biopsy studies presented at the meeting.
Liquid biopsy as a longitudinal tool
Liquid biopsy has been an active area of discussion at major oncology meetings for several years as it is increasingly used for assessing molecular residual disease (MRD), relapse risk, and treatment response. At AACR 2026, presentations largely focused on the parameters that determine whether ctDNA measurements are reliable enough to support clinical decisions. This includes sensitivity at very low variant allele fractions (VAF), run-to-run reproducibility, and the establishment of analytically validated thresholds for positivity and data interpretation.
A dedicated session on liquid biopsy performance standards, led by The Blood Profiling Atlas in Cancer (BLOODPAC), explored the criteria required for regulatory validation, including defining intended-use populations and target conditions, and evaluating data accuracy. These considerations are particularly relevant as ctDNA assays transition from exploratory biomarker work to clinical trial endpoints in the context of single and multi-cancer detection.
Demonstrating what longitudinal ctDNA monitoring can enable in practice, the TOMBOLA trial, a Danish multicenter study, evaluated ctDNA-guided immunotherapy following cystectomy in muscle-invasive bladder cancer. Patient-specific droplet digital PCR (ddPCR) assays targeting tumor-derived single nucleotide variants were used to monitor plasma ctDNA status in the postoperative period. Patients who tested ctDNA-positive received atezolizumab regardless of imaging findings, with the intent of intervening at a stage of minimal metastatic burden.
Preliminary data showed that ctDNA clearance following immunotherapy was observed in a substantial proportion of treated patients, and that ctDNA levels correlated with recurrence risk and treatment response. This positions ctDNA as a quantitative response biomarker with potential implications for treatment stratification.
At AACR, the researchers shared further insights from the TOMBOLA trial, outlining the results from a comparative study between ddPCR and whole-genome sequencing (WGS). They found that, even though there was a high concordance in ctDNA detection in plasma between the two methods, 12 percent of the samples (particularly those with low tumor fractions) were only positive with ddPCR. This further demonstrates the power of this tool in the quantification of rare analytes.
Epigenetics and methylation move into the spotlight
Epigenetic markers, and DNA methylation in particular, also received substantial attention at AACR 2026. The topic reflects the growing recognition that mutation-based ctDNA analysis alone is insufficient for certain clinical contexts. Methylation patterns carry tissue-of-origin information that genetic alterations do not, and methylated cell-free (cf)DNA fragments can be detected in plasma even when tumor mutational burden is low. This is an important consideration in early-stage disease, where ctDNA fractions are often at the limit of detection for mutation-based assays.
Data presented at the meeting included work on integrated genomic and epigenomic ctDNA detection in colorectal cancer using multiplex ddPCR technology. The study showed that simultaneous profiling of somatic mutations and methylation markers improved sensitivity relative to either analyte type alone.
This approach showcases a broader trend in the field whereby multi-marker strategies that combine mutation and methylation data are used to increase the probability of detection, particularly at low tumor fractions. The analytical properties of ddPCR technology – which enables absolute quantification through Poisson statistics without reliance on a standard curve – make it well suited to the detection of methylated cfDNA at the low concentrations encountered in plasma.
MRD as a clinical and translational endpoint
The Discovery Science Plenary session, titled “The Next Frontier in Minimal Residual Disease: Solid Tumors,” aimed to showcase the technological advances behind MRD detection and its impact on therapeutic and disease outcomes, as well as biological mechanisms driving disease progression and drug resistance.
MRD detection has already influenced treatment strategies in hematologic malignancies, where assay sensitivity, reproducibility, and regulatory acceptance are more established. The abstract landscape at AACR 2026 suggested that solid tumor MRD is reaching a comparable level of research, with data spanning colorectal, lung, breast, and urothelial cancers. Several of those abstracts demonstrate how ddPCR technology can support MRD monitoring and targeted therapeutic strategies, including work on MRD detection and monitoring in solid tumors and hematologic malignancies presented in an exhibitor spotlight session.
Resistance tracking: earlier signals, clearer decisions
Another thread running through the meeting includes early resistance tracking during therapy. For well-defined molecular mechanisms of resistance – such as EGFR-driven non-small cell lung cancer or KRAS-mutant colorectal cancer – longitudinal ctDNA analysis enables the detection of emergent resistant clones prior to any changes detectable by imaging. However, as highlighted in multiple sessions during the meeting, the frequency of monitoring and the sensitivity threshold of the assay used have direct implications for the clinical utility of this approach.
The evolution of quantitative precision diagnostics
The scientific program at AACR 2026 reinforced that the translation of liquid biopsy from research to clinical practice is closer than ever, with longitudinal monitoring using ultra-sensitive tools proving to be a major driver behind these advancements. Next-generation sequencing continues to expand the scope of genomic discovery and plays an established role in novel target identification. Meanwhile, precise technologies that deliver rapid, reproducible, and interpretable quantitative results offer a complementary and, in certain monitoring contexts, more practical approach in oncology research.
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