Track: Liquid Biopsies in Early Cancer Detection

 Liquid Biopsies in Early Cancer Detection

Multi-Cancer Early Detection (MCED) Tests
MCED tests, like GRAIL’s Galleri, detect multiple cancer types from a single blood sample by analyzing ctDNA methylation patterns. These tests are designed to catch cancers before symptoms appear, often when tumors are not yet visible via imaging. In the CCGA study, Galleri demonstrated the ability to detect over 50 cancer types with a false positive rate below 1%. MCED tests promise to change the landscape of population-wide screening, but still require more real-world validation and integration into clinical guidelines.

ctDNA for Minimal Residual Disease (MRD) Monitoring
After curative-intent treatment, recurrence risk remains a concern. ctDNA assays can detect minimal residual disease (MRD)—small amounts of tumor DNA left in the body—weeks or months before recurrence appears on imaging. Trials like TRACERx and DYNAMIC have shown ctDNA to be a reliable MRD marker in lung and colon cancer. In breast cancer, MRD monitoring could soon guide adjuvant therapy duration and intensity. This approach enables personalized surveillance and earlier intervention, potentially improving survival and reducing overtreatment.

Early Breast Cancer Detection Using ctDNA and CTCs
Liquid biopsies are being explored for early breast cancer detection, especially in high-risk populations. While mammography remains the gold standard, ctDNA assays may identify genetic alterations or copy number variations before radiological signs appear. CTC detection is another avenue, as shown in studies like STIC CTC, which demonstrated that CTC count could guide therapy in HR+ breast cancer. While not yet approved for screening, integrating liquid biopsy into existing diagnostic pathways may enhance sensitivity, particularly in dense breast tissue.

FDA-Approved Liquid Biopsy Tests and Their Applications
Several liquid biopsy assays are now FDA-approved. For example, Guardant360 and FoundationOne Liquid CDx provide genomic profiling for advanced cancers, helping guide targeted therapies. The Signatera test is approved for MRD detection in colorectal cancer. These tests are increasingly used in lieu of repeat tissue biopsies, especially when tumors are inaccessible. Their adoption into NCCN guidelines and reimbursement policies is growing, making them more feasible for widespread clinical use across cancer types, including breast, lung, and prostate.

Advantages Over Traditional Biopsy Techniques
Traditional tissue biopsies are invasive, limited to a single tumor site, and may miss heterogeneity. Liquid biopsies offer a whole-body molecular snapshot, capturing subclonal mutations and evolving resistance. They can be performed repeatedly, facilitating dynamic treatment decisions. In metastatic disease, they can detect emergent mutations like ESR1, HER2, or KRAS, aiding therapy adjustments. Additionally, liquid biopsies are safer, less painful, and faster. These advantages make them particularly valuable in early detection, longitudinal monitoring, and response evaluation.

Limitations and Challenges of Liquid Biopsies
Despite promise, liquid biopsy has limitations, including lower sensitivity in early-stage cancers, variability in ctDNA shedding, and false positives from clonal hematopoiesis. Standardization of assays and regulatory frameworks are needed. Cost and insurance coverage also pose challenges to routine adoption. Studies such as the LUNAR and CIRCULATE programs aim to improve specificity and validate clinical utility. Addressing these hurdles is critical for integrating liquid biopsies into standard cancer screening and early diagnostic pathways.

Future Directions in Liquid Biopsy Research
Ongoing research is focused on combining multiple analytes (ctDNA + exosomes + proteins) for improved accuracy, developing ultra-sensitive sequencing platforms, and integrating AI for pattern recognition. Trials like PREVAIL and DETECT-A aim to assess the impact of liquid biopsy-based screening on survival. Cross-disciplinary collaborations are working toward decentralized access through point-of-care testing. As evidence builds, liquid biopsy is expected to become a cornerstone of early detection, risk stratification, and precision oncology.