TY - JOUR
T1 - Understanding EGFR heterogeneity in lung cancer
AU - Passaro, Antonio
AU - Malapelle, Umberto
AU - Del Re, Marzia
AU - Attili, Ilaria
AU - Russo, Alessandro
AU - Guerini-Rocco, Elena
AU - Fumagalli, Caterina
AU - Pisapia, Pasquale
AU - Pepe, Francesco
AU - De Luca, Caterina
AU - Cucchiara, Federico
AU - Troncone, Giancarlo
AU - Danesi, Romano
AU - Spaggiari, Lorenzo
AU - De Marinis, Filippo
AU - Rolfo, Christian
N1 - Funding Information:
Competing interests AP has received honoraria for consulting, advisory role or lectures from AstraZeneca, Agilent/Dako, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Pfizer and Roche Genentech. UM has received personal fees from Boehringer Ingelheim, Roche, MSD, Amgen, Merck and AstraZeneca. FDM has served in a consultant/advisory role for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, Novartis, Roche Genentech, Takeda and Pfizer. CR has received speakers’ bureau from AstraZeneca and MSD, a research grant from the Lung Cancer Research Foundation–Pfizer, and research support from Guardant Health and Biomark; has an advisory board role with ARCHER, Inivata and Merck Serono; and hasconsulted for Mylan and Oncopass.
Publisher Copyright:
©
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/16
Y1 - 2020/10/16
N2 - 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.
AB - 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.
KW - EGFR
KW - heterogeneity
KW - mutations
KW - NSCLC
UR - http://www.scopus.com/inward/record.url?scp=85093706325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85093706325&partnerID=8YFLogxK
U2 - 10.1136/esmoopen-2020-000919
DO - 10.1136/esmoopen-2020-000919
M3 - Review article
C2 - 33067323
AN - SCOPUS:85093706325
VL - 5
JO - ESMO Open
JF - ESMO Open
SN - 2059-7029
IS - 5
M1 - e000919
ER -