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Anticipating EGFR Targeting in Early Stages of Lung Cancer: Leave No Stone Unturned.

ABSTRACT: Background: The current treatment landscape of early stage lung cancer is rapidly evolving, particularly in EGFR mutant non-small cell lung cancer (NSCLC), where target therapy is moving to early stages. In the current review, we collected the available data exploring the impact of EGFR targeting in both neoadjuvant and adjuvant settings, underlying lights and shadows and discussing the existing open issues. Methods: We performed a comprehensive search using PubMed and the proceedings of major international meetings to identify neoadjuvant/adjuvant trials with EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Results: Limited data are available so far about the activity/efficacy of neoadjuvant TKIs in EGFR mutant NSCLC, with only modest downstaging and pathological complete response rates reported. Differently, the ADAURA trial already proposed osimertinib as a potential new standard of care in resected NSCLC harboring an activating EGFR mutation. Conclusion: Anticipating targeted therapy to early stage EGFR mutant NSCLC presents great opportunities but also meaningful challenges in the current therapeutic/diagnostic pathway of lung cancer care. Appropriate endpoint(s) selection for clinical trials, disease progression management, patients' and treatment selection, as well as need to address the feasibility of molecular profiling anticipation, represent crucial issues to face before innovation can move to early stages.

SUBMITTER: Belluomini L

PROVIDER: S-EPMC8535007 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Anticipating EGFR Targeting in Early Stages of Lung Cancer: Leave No Stone Unturned.

Belluomini Lorenzo L Riva Silvia Teresa ST Simbolo Michele M Nocini Riccardo R Trestini Ilaria I Avancini Alice A Tregnago Daniela D Ferrara Miriam Grazia MG Caldart Alberto A Dodi Alessandra A Caliò Anna A Bria Emilio E Scarpa Aldo A Milella Michele M Menis Jessica J Pilotto Sara S

Cells 20211007 10

Background: The current treatment landscape of early stage lung cancer is rapidly evolving, particularly in EGFR mutant non-small cell lung cancer (NSCLC), where target therapy is moving to early stages. In the current review, we collected the available data exploring the impact of EGFR targeting in both neoadjuvant and adjuvant settings, underlying lights and shadows and discussing the existing open issues. Methods: We performed a comprehensive search using Pu ...[more]

PMID: 34685665

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Project description:BackgroundThe hyperarid core of the Atacama Desert is an extremely harsh environment thought to be colonized by only a few heterotrophic bacterial species. Current concepts for understanding this extreme ecosystem are mainly based on the diversity of these few species, yet a substantial area of the Atacama Desert hyperarid topsoil is covered by expansive boulder accumulations, whose underlying microbiomes have not been investigated so far. With the hypothesis that these sheltered soils harbor uniquely adapted microbiomes, we compared metagenomes and geochemistry between soils below and beside boulders across three distantly located boulder accumulations in the Atacama Desert hyperarid core.ResultsGenome-resolved metagenomics of eleven samples revealed substantially different microbial communities in soils below and beside boulders, despite the presence of shared species. Archaea were found in significantly higher relative abundance below the boulders across all samples within distances of up to 205 km. These key taxa belong to a novel genus of ammonia-oxidizing Thaumarchaeota, Candidatus Nitrosodeserticola. We resolved eight mid-to-high quality genomes of this genus and used comparative genomics to analyze its pangenome and site-specific adaptations. Ca. Nitrosodeserticola genomes contain genes for ammonia oxidation, the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway, and acetate utilization indicating a chemolithoautotrophic and mixotrophic lifestyle. They also possess the capacity for tolerating extreme environmental conditions as highlighted by the presence of genes against oxidative stress and DNA damage. Site-specific adaptations of the genomes included the presence of additional genes for heavy metal transporters, multiple types of ATP synthases, and divergent genes for aquaporins.ConclusionWe provide the first genomic characterization of hyperarid soil microbiomes below the boulders in the Atacama Desert, and report abundant and highly adapted Thaumarchaeaota with ammonia oxidation and carbon fixation potential. Ca. Nitrosodeserticola genomes provide the first metabolic and physiological insight into a thaumarchaeal lineage found in globally distributed terrestrial habitats characterized by various environmental stresses. We consequently expand not only the known genetic repertoire of Thaumarchaeota but also the diversity and microbiome functioning in hyperarid ecosystems. Video Abstract.

Dataset Information

Anticipating EGFR Targeting in Early Stages of Lung Cancer: Leave No Stone Unturned.

Publications

Anticipating EGFR Targeting in Early Stages of Lung Cancer: Leave No Stone Unturned.

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