Liquid Biopsy for the Detection of Resistance Mechanisms in NSCLC: Comparison of Different Blood Biomarkers

Abstract

The use of targeted agents and immunotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC) has made it mandatory to characterize tumor tissue for patient selection. Moreover, the development of agents that are active against specific resistance mechanisms arising during treatment make it equally important to characterize the tumor tissue at progression by performing tissue re-biopsy. Given that tumor tissue is not always available for molecular characterization due to the paucity of diagnostic specimens or problems relating to the carrying out of invasive procedures, the use of liquid biopsy represents a valid approach to overcoming these difficulties. The most common material used for liquid biopsy in this setting is plasma-derived cell free DNA (cfDNA), which originates from cells undergoing apoptosis or necrosis. However, other sources of tumor material can be considered, such as extracellular vesicle (EV)-derived nucleic acids, which are actively secreted from living cells and closely correspond to tumor dynamics. In this review, we discuss the role of liquid biopsy in the therapeutic management of NSCLC with particular regard to targeted therapy and immunotherapy, and analyze the pros and cons of the different types of samples used in this context.

BRAF V600E Detection in Liquid Biopsies from Pediatric Central Nervous System Tumors

“…One possible explanation is that those tumors rarely metastasize outside the CNS [33], so ctDNA released to the bloodstream is restricted and makes minority allele detection more difficult [34]. Nevertheless, it could be useful when a solid biopsy is not available and for therapy response prediction [35], as has been approved by the FDA in NSCLC patients [9], in which values obtained for EGFR mutations were 100% of specificity and 65.7% of sensitivity [36].…”

Immuno-Oncology Biomarkers for Personalized Immunotherapy in Breast Cancer

“…The utility of ctDNA for assessment of TMBs delivers support for limited or inaccessible tissue samples to improve therapeutic decisions for some cancers (Gandara et al, 2018); however, this is highly dependent on the selection of the gene-targeted panel to evaluate TMBs, and most probably needs to be customized for each cancer type. In addition, the efficiency and precision of the assay using ctDNA to depict TMB is dependent on high coverage of the assay (Gandara et al, 2018;Georgiadis et al, 2019;Pasini and Ulivi, 2019). For breast cancer a NGS panel of mutations associated with 76 target genes, MammaSeq TM , have been recently developed with applicable use of ctDNA.…”

Patologia molecular em cancro do pulmão: Evolução e contributos

“…A introdução da biópsia líquida na prática clínica em cancro do pulmão, através do estudo de ADN livre em circulação (cfDNA), traduziu -se na estratégia ideal para monitorização da resposta ao tratamento e deteção atempada do início dos mecanismos de resistência, nomeadamente, na identificação da mutação de resistência T790M. A possibilidade de identificar mecanismos de resistência durante o tratamento pode ajudar a identificar a progressão da doença mais cedo e, deste modo, melhorar a personalização do tratamento destes doentes 36,37 .…”