An integrative functional genomics approach reveals EGLN1 as a novel therapeutic target in KRAS mutated lung adenocarcinoma

Reggiani, Francesca; Sauta, Elisabetta; Torricelli, Federica; Zanetti, Eleonora; Tagliavini, Elena; Santandrea, Giacomo; Gobbi, Giulia; Damia, Giovanna; Bellazzi, Riccardo; Ambrosetti, Davide Carlo; Ciarrocchi, Alessia; Sancisi, Valentina

doi:10.1186/s12943-021-01357-z

Cited by 7 publications

(2 citation statements)

References 17 publications

(14 reference statements)

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“…Recent study also showed that elevated EGLN1 expression might be a valuable biomarker of poor prognosis in patients with LUAD, but not in LUSC (36). Moreover, Reggiani et al identified and validated that the EGLN1 gene might be a novel therapeutic target, preferentially associated with KRAS-mutated LUAD by integrating functional genomic analysis, in vitro data of cancer cell lines, gene druggability data, and patients' transcriptomic and mutational data (37). Mechanistically, EGLN1 pro-oncogenic activity was partially dependent on HIF1A.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Novel Ferroptosis-Related Gene Signature for Predicting Survival of Patients With Lung Adenocarcinoma

Song

Wang

et al. 2022

Front. Oncol.

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Lung adenocarcinoma (LUAD) is the most diagnosed subtype of lung cancer; ferroptosis is widely involved in the pathological cell death associated with various cancers, including lung cancer. However, the comprehensive relationship between ferroptosis and LUAD is little known in molecular levels until now. In the present study, 513 LUAD patients could be aggregated into three clusters by consensus clustering based on RNA sequencing data of 291 ferroptosis-related genes (FRGs) in The Cancer Genome Atlas (TCGA) database; cluster2 had significant survival advantage compared to the other two clusters. A novel prognostic model of 8 differential FRGs was constructed to effectively divide LUAD patients into high- or low-risk group according to the risk scores by the Cox and LASSO regression analyses. The overall survival of LUAD patients in the high-risk group was significantly worse in the TCGA and GEO cohorts. Moreover, patients with radiation therapy or high clinical stage had obviously higher risk scores. We validated the differential mRNA and protein expression of four FRGs in paired tumor and normal samples from our clinical cohort. Our study constructed a novel FRG signature to predict the prognosis of LUAD patients, which might provide a new prognostic tool and potential therapeutic targets for LUAD.

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Section: Discussionmentioning

confidence: 99%

Construction of a Novel Ferroptosis-Related Gene Signature for Predicting Survival of Patients With Lung Adenocarcinoma

Song

Wang

et al. 2022

Front. Oncol.

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“…These new therapeutic strategies associate or will associate different combinations of molecules, including some SHP2 inhibitors or MEK inhibitors together with KRAS G12C specific inhibitors [ 130 , 240 , 241 , 242 , 243 , 244 , 245 ]. Other molecules targeting KRAS mutations have been tested or are ongoing, such as those targeting mTOR, IGF1R, FASN, or EGLN1 in association with inhibitors targeting KRAS G12C mutations, or those that modify glutamine metabolism [ 246 , 247 ]. Moreover, new drugs targeting other KRAS subtype mutations, such as KRAS G12D, are under evaluation in vitro or in clinical trials [ 246 , 248 , 249 ].…”

Section: Perspectivesmentioning

confidence: 99%

Daily Practice Assessment of KRAS Status in NSCLC Patients: A New Challenge for the Thoracic Pathologist Is Right around the Corner

Bontoux

Hofman

Brest

et al. 2022

Cancers

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KRAS mutations are among the most frequent genomic alterations identified in non-squamous non-small cell lung carcinomas (NS-NSCLC), notably in lung adenocarcinomas. In most cases, these mutations are mutually exclusive, with different genomic alterations currently known to be sensitive to therapies targeting EGFR, ALK, BRAF, ROS1, and NTRK. Recently, several promising clinical trials targeting KRAS mutations, particularly for KRAS G12C-mutated NSCLC, have established new hope for better treatment of patients. In parallel, other studies have shown that NSCLC harboring co-mutations in KRAS and STK11 or KEAP1 have demonstrated primary resistance to immune checkpoint inhibitors. Thus, the assessment of the KRAS status in advanced-stage NS-NSCLC has become essential to setting up an optimal therapeutic strategy in these patients. This stimulated the development of new algorithms for the management of NSCLC samples in pathology laboratories and conditioned reorganization of optimal health care of lung cancer patients by the thoracic pathologists. This review addresses the recent data concerning the detection of KRAS mutations in NSCLC and focuses on the new challenges facing pathologists in daily practice for KRAS status assessment.

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The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation

et al. 2022

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An integrative functional genomics approach reveals EGLN1 as a novel therapeutic target in KRAS mutated lung adenocarcinoma

Cited by 7 publications

References 17 publications

Construction of a Novel Ferroptosis-Related Gene Signature for Predicting Survival of Patients With Lung Adenocarcinoma

Construction of a Novel Ferroptosis-Related Gene Signature for Predicting Survival of Patients With Lung Adenocarcinoma

Daily Practice Assessment of KRAS Status in NSCLC Patients: A New Challenge for the Thoracic Pathologist Is Right around the Corner

The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation

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