Understanding EGFR heterogeneity in lung cancer
| Autor: | Francesco Pepe, Elena Guerini-Rocco, Caterina Fumagalli, Ilaria Attili, Antonio Passaro, Filippo de Marinis, Pasquale Pisapia, Caterina De Luca, Romano Danesi, Federico Cucchiara, Umberto Malapelle, Marzia Del Re, Christian Rolfo, Lorenzo Spaggiari, Giancarlo Troncone, Alessandro Russo |
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| Přispěvatelé: | Passaro, A., Malapelle, U., Del Re, M., Attili, I., Russo, A., Guerini-Rocco, E., Fumagalli, C., Pisapia, P., Pepe, F., De Luca, C., Cucchiara, F., Troncone, G., Danesi, R., Spaggiari, L., De Marinis, F., Rolfo, C. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Lung Neoplasms EGFR Review Disease Biology Bioinformatics NSCLC Somatic evolution in cancer lcsh:RC254-282 Carcinoma Non-Small-Cell Lung Tumor Microenvironment medicine Humans Epidermal growth factor receptor Lung cancer Protein Kinase Inhibitors Genotyping Clinical study design Cancer mutations medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ErbB Receptors heterogeneity Oncology Genomic Profile biology.protein mutation |
| Zdroj: | ESMO Open, Vol 5, Iss 5 (2020) ESMO Open |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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