Liquid biopsy and ctDNA: the winner tandem

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Precision medicine is an approach to patient care that allows doctors to select treatments that are most likely to help patients based on a genetic understanding of their disease. Recent advances in science and technology have helped speed up the pace of this area of research, making precision medicine the new paradigm of healthcare.

In recent years, there has been a revolutionary expansion in technologic advances in cancer medicine. State-of-the-art next-generation DNA sequencing (NGS) and genomics bioinformatics analysis allows a shift from microscopic levels of histologic diagnostics to molecular genomics levels of cancer molecular diagnostic. This change has enabled better treatment selection, reduces adverse events, rendering in an improvement of patient´s quality of life and survival.

Traditional tumor biopsy is still considered the gold standard in diagnostic oncology. However, the static nature of this technique is one of its main limits, because is not able to follow the dynamics adaptations triggered by anticancer therapies. Not to comment on the clinical complications of tissue sampling and its impact on patient´s life. As body fluids can be easily obtained in a non-invasive way, liquid biopsy is an attractive alternative approach that allows, among other things, a dynamic assessment of specific molecular markers, intercept the onset of disease recurrence, treatment resistance, potentially predict response and prognosis. Tumor cells are constantly releasing to the bloodstream DNA of different forms, such as cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), micro RNAs (miRNAs), and more. These sources could be used for rapid and effective molecular characterization of the tumor molecular profile.

The utility of liquid biopsy and ctDNA analysis in breast cancer would be the base for the development of personalized medicine in the future. In the neoadjuvant and adjuvant settings, because of its curative nature, the possibility of detecting minimal disease is vital to assess treatment response and guide therapeutic options. In addition, for early detection of recurrence, the identification of useful biomarkers to detect micrometastatic disease or post-surgical tumor residues is paramount. ctDNA analysis might play an important role in these scenarios. In the metastatic disease, liquid biopsy has the potential to overcome several practical issues such as hardly accessible primary and metastatic lesions, patient´s refusal to invasive procedures, not feasible serial sampling or inadequate or insufficient material for molecular analysis. In addition, because ctDNA levels are associated with tumor burden, a longitudinal plasma-based assessment may represent an indirect measure of treatment response and predict clinical outcome. Furthermore, ctDNA dynamics not only has a significant prognostic impact but also has a higher sensitivity with respect to tumor markers, making possible to anticipate imaging-based disease progression.

With the current expansion of clinical applications of genomics-matching personalized cancer therapy, it has also become increasingly evident that the need to obtain a large amount of tumor tissue through invasive tumor-needle or surgical biopsy procedures is untenable. In the last years, liquid biopsy techniques as a source of material for assaying ctDNAs for genetic/genomic marker alterations are being increasingly applied. Undoubtedly, liquid biopsy and ctDNA analysis are beginning to pave the way to a growingly individualized cancer care.


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