In the era of precision oncology, liquid biopsy technologies are reshaping the landscape of cancer diagnosis and treatment. Among them, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and traditional tumor markers are hailed as the "three musketeers of liquid biopsy." What exactly are they? What information can each provide for patients? This article will clarify everything in one go.

Tumor Markers

Tumor markers are proteins, carbohydrates, or other substances secreted by tumor cells or produced by the body’s immune response — examples include CEA and CA19-9.

The advantages of tumor marker testing are low cost and ease of operation. However, they suffer from insufficient specificity and sensitivity — inflammation and benign lesions can cause false positives, while early-stage tumors often do not elevate these markers, leading to missed diagnoses. An expert consensus states: "Traditional serum tumor markers have low positive predictive value in early cancer screening and cannot meet the demands of precision diagnosis" [1].

Circulating Tumor DNA (ctDNA)

ctDNA refers to fragmented DNA released into the bloodstream by apoptotic or necrotic tumor cells, carrying tumor-specific genetic mutations, methylation patterns, and other molecular information.

The advantage of ctDNA testing is its ability to capture the real-time genomic landscape of the tumor, guiding targeted therapy. However, challenges are evident: release levels are extremely low in early-stage tumors, and ctDNA cannot provide complete cellular morphology or functional information, nor can it easily assess drug sensitivity phenotypes [2].

Circulating Tumor Cells (CTCs)

CTCs are tumor cells that detach from primary or metastatic tumors, enter the bloodstream, and retain intact cellular structure — they are the direct "seeds" of hematogenous metastasis.

Compared to the other two, CTC testing offers unique and irreplaceable advantages:

• Integrity: CTCs are whole cells, simultaneously providing genomic, transcriptomic, protein expression, and even cytomorphological information.

• Viability: They can be cultured in vitro and tested for drug sensitivity, guiding personalized treatment.

• Functional validation: CTCs can directly demonstrate metastatic potential — they are true "seeds of metastasis."

• Dynamic monitoring: Changes in CTC count are highly correlated with treatment response and can indicate progression weeks earlier than imaging.

As the cytological dimension of liquid biopsy, CTCs provide functional information and phenotypic evidence that cannot be obtained from ctDNA or protein markers. Therefore, CTCs are applicable in the following areas:

• Early screening: Assessing cancer risk via CTC counts.

• Treatment monitoring: Evaluating therapeutic efficacy through CTC levels.

• Recurrence and metastasis monitoring: Rising CTC counts may indicate recurrence or metastasis.

• Personalized therapy: Detecting target expression on CTCs to guide precision treatment.

Summary

The three technologies are not mutually exclusive but complementary. However, if you need a testing method that combines information integrity, real-time dynamics, and clinical guidance value, circulating tumor cell testing is undoubtedly the better choice.

References:
1. Committee of Tumor Markers, China Anti-Cancer Association. Expert Consensus on Clinical Application of Tumor Markers (2022 Edition).

2. Wan JCM, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-238.