Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Abstract

Non-small cell lung cancer is one leading cause of death worldwide, and patients would greatly benefit from an early diagnosis. Since targeted and immunotherapies have emerged as novel approaches for more tailored treatments, repeated assessments of the tumor biology have become pivotal to drive clinical decisions. Currently, tumor tissue biopsy is the gold standard to investigate potentially actionable biomarkers, but this procedure is invasive and may prove inadequate to represent the whole malignancy. In this regard, liquid biopsy represents a minimally invasive and more comprehensive option for early detection and investigation of this tumor. Today, cell-free DNA is the only approved circulating marker to select patients for a targeted therapy. Conversely, the other tumor-derived markers (i.e., circulating tumor cells, miRNAs, exosomes, and tumor educated platelets) are still at a pre-clinical phase, although they show promising results for their application in screening programs or as prognostic/predictive biomarkers. The main challenges for their clinical translation are the lack of reliable cutoffs and, especially for miRNAs, the great variability among the studies. Moreover, no established tool has been approved for circulating tumor cells and exosome isolation. Finally, large prospective clinical trials are mandatory to provide evidence of their clinical utility.

Precision Medicine for NSCLC in the Era of Immunotherapy: New Biomarkers to Select the Most Suitable Treatment or the Most Suitable Patient

“…These small vesicles, released by an endosomal maturation, carry biomolecules such as genetic material, including DNA, mRNAs, miRNAs and other noncoding RNAs, as well as proteins [172]. Exosomes can be found in various body fluids, such as the blood, sputum, urine, or malignant effusions, and they play a pivotal role in intercellular communication [173]. Interestingly, tumor-derived exosomes bearing their molecular and genetic cargo may reflect the composition of tumor cells.…”

Novel Liquid Biomarker Panels for A Very Early Response Capturing of NSCLC Therapies in Advanced Stages

“…Many different markers have been described to be useful individually for diagnosis or prediction of NSCLC therapies [36]. However, due to complex biological changes in tumor and patients' metabolism, no single biomarker has entered clinical routine.…”

Molecular diagnostics in oncology: new trends

“…В настоящее время жидкостная биопсия уже используется в практической онкологии для анализа мутаций EGFR Т790М у пациентов, получающих лечение гефитинибом, эрлотинибом или афатинибом. На основе результатов данного теста принимают решение о целесообразности назначения ингибитора EGFR третьего поколения -препарата осимертиниба [42,43]. Ожидается, что в среднесрочной перспективе сфера использования жидкостной био псии заметно расширится.…”