Understanding the Mechanisms of Resistance in EGFR-Positive NSCLC: From Tissue to Liquid Biopsy to Guide Treatment Strategy

Marzia Del Re, Stefania Crucitta, Giulia Gianfilippo, Antonio Passaro, Iacopo Petrini, Giuliana Restante, Angela Michelucci, Stefano Fogli, Filippo de Marinis, Camillo Porta, Antonio Chella, Romano Danesi

Research output: Contribution to journalReview articlepeer-review


Liquid biopsy has emerged as an alternative source of nucleic acids for the management of Epidermal Growth Factor Receptor (EGFR)-mutant non-Small Cell Lung Cancer (NSCLC). The use of circulating cell-free DNA (cfDNA) has been recently introduced in clinical practice, resulting in the improvement of the identification of druggable EGFR mutations for the diagnosis and monitoring of response to targeted therapy. EGFR-dependent (T790M and C797S mutations) and independent (Mesenchymal Epithelial Transition [MET] gene amplification, Kirsten Rat Sarcoma [KRAS], Phosphatidyl-Inositol 4,5-bisphosphate 3-Kinase Catalytic subunit Alpha isoform [PI3KCA], and RAF murine sarcoma viral oncogene homolog B1 [BRAF] gene mutations) mechanisms of resistance to EGFR tyrosine kinase inhibitors (TKIs) have been evaluated in plasma samples from NSCLC patients using highly sensitive methods (i.e., digital droplet PCR, Next Generation Sequencing), allowing for the switch to other therapies. Therefore, liquid biopsy is a non-invasive method able to detect the molecular dynamic changes that occur under the pressure of treatment, and to capture tumor heterogeneity more efficiently than is allowed by tissue biopsy. This review addresses how liquid biopsy may be used to guide the choice of treatment strategy in EGFR-mutant NSCLC.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Issue number16
Publication statusPublished - Aug 14 2019


  • Animals
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Circulating Tumor DNA
  • Clinical Decision-Making
  • Disease Management
  • Drug Resistance, Neoplasm/genetics
  • ErbB Receptors/genetics
  • Humans
  • Liquid Biopsy
  • Lung Neoplasms/drug therapy
  • Molecular Targeted Therapy
  • Mutation
  • Protein Kinase Inhibitors/pharmacology


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