Cancer Biomarkers: Advancements using blood-derived biospecimens

June 9, 2025

Cancer continues to challenge medical science, but recent years have brought remarkable advances in how we detect, monitor, and treat it. Central to these improvements is a growing focus on blood-based sampling, which opens new avenues for finding and acting upon cancer biomarkers. The push toward minimally invasive, precision-guided care puts blood-derived samples—such as plasma, serum, whole blood, peripheral blood mononuclear cells (PBMCs), and circulating tumor cells (CTCs)—in the spotlight.

Discovering Cancer Biomarkers in Blood Samples

Traditional cancer diagnosis often depends on tissue biopsies and imaging. These can be invasive, risky, and sometimes not feasible, especially if tumors are deep inside the body or in critical locations. Blood, however, holds unique promise for discovering cancer biomarkers. Accessible with a simple draw, it provides a window into the body’s real-time molecular landscape.

Cancer biomarker research embracing blood-based samples is driven by several powerful motivations:

Minimal invasiveness: Lower risk and discomfort for patients.
Dynamic insight: The ability to capture changes in tumor cells and their microenvironment during disease progression or treatment.
Scalability: Enabling large-scale screening and monitoring across diverse populations.

Let’s untangle how different blood-based samples help us track, diagnose, and shape cancer care.

Cancer Biomarker Donor - Sanguine Biosciences

Whole Blood: The Raw Material

Sometimes, analysis doesn’t begin with separated plasma or serum. Whole blood testing preserves all cell types, plasma, and serum constituents just as they exist in the body. Genomic, transcriptomic, and metabolomic assays can be performed directly from a drop or tube of whole blood, making this approach suitable for point-of-care diagnostics and comprehensive omics studies.

Whole blood is particularly handy for:

Circulating cell analyses: Assessing the distribution of different white blood cells, which can fluctuate in cancer and predict prognosis.
Host response profiling: Investigating how the immune system is responding to a tumor or to treatments such as immunotherapy.

Plasma vs. Serum: Nuances that Matter for Cancer Biomarkers

Two common types of blood-derived samples—plasma and serum—may appear similar, but their subtle differences play a big role in discovering and characterizing cancer biomarkers.

Property	Plasma	Serum
Definition	Clear fluid remaining after centrifuging blood with anticoagulants	Clear fluid after blood coagulates and is centrifuged
Key Components	Water, proteins (including clotting factors), hormones, metabolites, cell-free nucleic acids (cfDNA/cfRNA)	Similar to plasma but without most clotting factors
Preparation	Requires anticoagulants (e.g., EDTA, heparin)	No anticoagulant; allows natural clotting to occur
Typical Uses	Liquid biopsy, circulating tumor DNA (ctDNA), proteomic studies, biomarker discovery	Serological tests, some metabolomic and protein biomarker research
Advantages	Reflects circulating markers in their native state, fewer background signals from clotting	Easier sample processing in some contexts, higher yield of certain proteins

Researchers often prefer plasma for studying cancer biomarkers because it retains clotting factors and more closely mirrors the “true” biochemical environment of circulating blood. Yet, serum remains valuable for protein analyses where clotting-related factors are not a concern.

Plasma: A Dynamic Reservoir for Cancer Biomarker Discovery

The process is surprisingly simple: blood is drawn, anticoagulated, and spun down. This yields plasma brimming with cell-free DNA, RNA, proteins, metabolites, and extracellular vesicles—molecules emitted not only by healthy cells but, crucially, by tumor cells. This is the foundation of the “liquid biopsy” revolution.

Key applications in oncology include:

Circulating tumor DNA (ctDNA): Tumor cells shed small fragments of DNA into the bloodstream. Sensitive assays can detect mutations, amplifications, and methylation changes that guide therapy and reveal resistance.
Cell-free RNA (cfRNA): Offers clues about gene expression, splicing variants, and tumor heterogeneity.
Protein biomarker panels: Large multiplex screens are starting to tease out early warning signals for various cancers — often before symptoms arise or imaging detects a mass.

By serially sampling plasma, clinicians can monitor tumor evolution, track response to treatment, and spot signs of relapse months ahead of conventional approaches.

Serum: Unlocking Insights into Cancer Biomarkers

Serum, though slightly depleted in certain molecules, compensates with well-established workflows and robust historical datasets. Diagnostic tests for cancer antigens—like PSA for prostate cancer, CA-125 for ovarian cancer, or CEA for colon cancer—often use serum.

Some studies find serum preferable for detecting high-abundance proteins, autoantibodies, or metabolic profiles linked to cancer risk. The process of clotting may even expose or “unmask” antigenic proteins otherwise hidden in plasma.

Peripheral Blood Mononuclear Cells (PBMCs): Unveiling the Immune Landscape

Extracted from whole blood via a density gradient, PBMCs include lymphocytes (T cells, B cells, natural killer cells) and monocytes. Their analysis sheds light on:

Immune surveillance: The ability (or failure) of the immune system to detect and destroy tumor cells.
Immunotherapy response: Identifying cellular markers that predict success with emerging treatments.
Tumor-immune interaction: Unraveling immune profiles that distinguish aggressive cancers from more benign forms.

Single-cell sequencing and advanced flow cytometry now enable a breathtaking level of detail, mapping immune cell states and functions from a simple blood sample.

Circulating Tumor Cells (CTCs): Cancer’s Messengers

Among the most exciting developments is the capture and characterization of circulating tumor cells. These are rare cells shed by tumors that travel in the bloodstream, sometimes seeding distant metastases.

Detecting and studying CTCs is no trivial task. They’re vastly outnumbered by blood cells, requiring intricate enrichment techniques—often based on unique surface markers or physical properties. Once isolated, CTCs offer a treasure trove of information, including:

Tumor genotype and phenotype: Analysis of mutations, gene expression, protein markers, and sensitivity to drugs.
Metastatic potential: Certain features on CTCs may signal likelihood of spread or recurrence.
Real-time monitoring: Sequential counts and analysis over time help refine treatment decisions.

Since CTCs represent viable tumor cells, they provide direct evidence of ongoing disease activity and may even be “avatars” to test potential therapies ex vivo.

Current Challenges and Points of Progress

Blood-based cancer biomarkers generate enthusiasm, but reality brings technical and biological complications:

Sensitivity and specificity: Detecting mutations or rare cells with high confidence is challenging amid overwhelming signals from normal blood constituents.
Standardization: Variability in sample handling, processing, and analytical platforms can hinder reproducibility and clinical adoption.
Integration: Combining information from plasma, serum, PBMCs, and CTCs to build a coherent and actionable profile presents both computational and logistical obstacles.

Nonetheless, advances in molecular biology, digital PCR, next-generation sequencing, and bioinformatics are closing these gaps. Hospitals and diagnostic labs increasingly employ algorithms that integrate signals from multifaceted blood-based tests to direct patient care.

Emerging Frontiers: Multi-Analyte Testing

The future is not likely limited to a single biomarker or blood component. The next leap forward pairs diverse analytes into precision algorithms, improving early cancer detection, characterization, and personalized therapy. Projects underway gather plasma DNA, serum proteins, CTC counts, and immune cell profiles to generate “digital twins” of each patient—biology mapped with an unprecedented level of detail.

Imagine screening tests flagging cancer in its earliest stages, routine blood tests tracking microscopic disease, and dynamically updated treatment plans steered by real-time molecular signals. This multi-analyte vision promises more reliable, comprehensive cancer care, shifting the paradigm away from one-size-fits-all to truly personalized medicine.

Increasing Participation and Impact

Perhaps one of the most understated benefits is facilitating patient engagement. Blood draws are far less daunting than surgical biopsies or repeated imaging. This means more frequent sampling, better disease tracking, and higher willingness among people at risk or under surveillance to participate in screening and monitoring.

Large, population-level research studies also benefit. With blood sampling, researchers build richer biobanks that accelerate discovery, validation, and translation of new biomarkers into everyday clinical practice.

A New Era in Cancer Diagnostics

The convergence of blood-based sampling, advanced molecular assays, and data science is driving a steady shift in oncology. These methods don’t just promise earlier detection, better risk stratification, and closer monitoring; they also empower a deeper, person-specific grasp of cancer biology.

Whether through plasma’s cell-free DNA, the protein-rich world of serum, the immune insight from PBMCs, or rare clues from CTCs, blood samples are reshaping every phase of the cancer journey.

The horizon for cancer biomarker research has never been brighter or more filled with possibility. Blood, once just a passive witness to disease, is now at the center of a revolution in how we find, interpret, and beat cancer.