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Late-stage cancer diagnosis often limits treatment options and leads to unfavorable outcomes. Patients with metastatic solid cancers face limited curative options, underscoring the importance of early neoplasia detection for improved outcomes.

Histopathology has long been the gold standard for cancer diagnosis. While biopsies provide valuable samples, they have limitations in revealing tumor heterogeneity and are obtained when clinical evidence emerges, limiting early diagnosis potential.

Around 20 years ago, detecting circulating tumor cells (CTC) predicted survival in metastatic breast cancer patients starting new treatment lines, indicating CTC’s potential in staging advanced disease. Subsequently, liquid biopsy research expanded rapidly, exploring biomarkers in various body fluids for solid tumor assessment. Liquid biopsies are minimally invasive and easy to use, monitor treatment response, tracks the progression of the disease and can be helpful in identifying early relapse. It captures material from primary and metastatic sites, offering a more comprehensive view of tumor cell population compared to tissue biopsy.


The understanding of metastasis has shifted from linear progression to a more intricate set of concurrent processes. Disseminated tumor cells (DTC) in the bone marrow have challenged the conventional view of metastasis, suggesting that new phenotypes arise concurrently as old behaviours are abandoned. The initiation of metastasis is intricately influenced by tumor micro-environments, introducing complexity into the process. Notably, the detection of a significant number of circulating tumor cells (CTC) in comparison to the relatively few metastases indicates the early diffusion of tumor cells, underscoring their pivotal role.

The phenomenon of early dissemination continues to perplex researchers.  As cases of tumor resection followed by delayed metastasis might involve dormant DTC resulting from residual disease or clinically undetectable micrometastases. The presence of these dormant DTC could contribute to the delay in metastasis detection, subsequently delaying prognosis.

The potential for CTC to facilitate metastasis has prompted comprehensive biomarker research. Clusters of CTC have shown heightened metastatic capacity in contrast to individual CTC. Furthermore, the assessment of genetics, epigenetics, and protein levels has shed light on the mechanisms behind metastasis.

The utility of CTC in early relapse, coupled with their association with aggressive tumors, presents a strategic advantage over other biomarkers. This advantage translates into improved prospects for therapeutic intervention and durable remission rates.

References:
Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer
Systems Biology of Cancer Metastasis
Medscape