Understanding EGFR heterogeneity in lung cancer

Antonio Passaro, Umberto Malapelle, Marzia Del Re, Ilaria Attili, Alessandro Russo, Elena Guerini-Rocco, Caterina Fumagalli, Pasquale Pisapia, Francesco Pepe, Caterina De Luca, Federico Cucchiara, Giancarlo Troncone, Romano Danesi, Lorenzo Spaggiari, Filippo De Marinis, Christian Rolfo

Research output: Contribution to journalReview articlepeer-review


The advances in understanding the inherited biological mechanisms of non-small cell lung cancer harbouring epidermal growth factor receptor (EGFR) mutations led to a significant improvement in the outcomes of patients treated with EGFR tyrosine kinase inhibitors. Despite these clinically impressive results, clinical results are not always uniform, suggesting the need for deepening the molecular heterogeneity of this molecularly defined subgroup of patients beyond the clinical and biological surface. The availability of tissue and blood-based tumour genotyping allows us to improve the understanding of molecular and genetic intratumor heterogeneity, driving the measurement of clonal evaluation in patients with lung cancer carrying EGFR mutations. Genetic diversification, clonal expansion and selection are highly variable patterns of genetic diversity, resulting in different biological entities, also a prerequisite for Darwinian selection and therapeutic failure. Such emerging pieces of evidence on the genetic diversity, including adaptive and immunomodulated aspects, provide further evidence for the role of the tumour microenvironment (TME) in drug-resistance and immune-mediated mechanisms. Matching in daily clinical practice, the detailed genomic profile of lung cancer disease and tracking the clonal evolution could be the way to individualise the further target treatments in EGFR-positive disease. Characterising the tumour and immune microenvironment during the time of the cancer evaluation could be the way forward for the qualitative leap needed from bench to bedside. Such a daring approach, aiming at personalising treatment selection in order to exploit the TME properties and weaken tumour adaptivity, should be integrated into clinical trial design to optimise patient outcome.

Original languageEnglish
Article numbere000919
JournalESMO Open
Issue number5
Publication statusPublished - Oct 16 2020


  • EGFR
  • heterogeneity
  • mutations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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