Non‐small cell lung cancer with <scp><i>EGFR</i></scp> (<scp>L858R</scp> and <scp>E709X</scp>) and <scp>CNNB1</scp> mutations responded to afatinib

Kunishige, Michihiro; Ichihara, Seiya; Kadota, Naoki; Okano, Yasuaki; Machida, Hisanori; Hatakeyama, Nobuo; Naruse, Keishi; Shinohara, Tsutomu; Takeuchi, Eiji

doi:10.1111/1759-7714.14775

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…The copyright holder for this this version posted March 13, 2024. ; https://doi.org/10.1101/2024.03.11.24304129 doi: medRxiv preprint reports or small series studies [67][68][69][70][71]. In vitro experiments using G719X mutant cell lines and patient-derived xenografts (PDX) demonstrated that osimertinib effectively inhibits signaling pathways and cellular growth, leading to sustained tumor growth inhibition [72].…”

Section: Discussionmentioning

confidence: 99%

“…Limited knowledge exists from G719X, mostly based on isolated case reports or small series studies [62][63][64][65][66]. In vitro experiments using G719X mutant cell lines and patient-derived xenografts (PDX) demonstrated that osimertinib effectively inhibits signaling pathways and cellular growth, leading to sustained tumor growth inhibition [67].…”

Section: Discussionmentioning

confidence: 99%

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Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

Zhang,

Liu,

Wang

et al. 2024

Preprint

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Air pollution significantly impact lung cancer progression, but there is a lack of a comprehensive molecular characterization of clinical samples associated with air pollution. Here, we performed a proteogenomic analysis of lung adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke is the primary contributor to the high lung cancer incidence. Genomic mutation analysis revealed XWLC as a distinct subtype of LUAD separate from cases associated with smoking or endogenous factors. Mutational signature analysis suggested that Benzo[a]pyrene (BaP) is the major risk factor in XWLC. The BaP-induced mutation hotspot, EGFR-G719X, was present in 20% of XWLC which endowed XWLC with elevated MAPK pathway activations and worse outcomes compared to commonEGFRmutations. Multi-omics clustering of XWLC identified four clinically relevant subtypes. These subgroups exhibited distinct features in biological processes, genetic alterations, metabolism demands, immune landscape, tumor microbiota composition and radiomic features. Finally,MAD1 and TPRNwere identified as novel potential therapeutic targets in XWLC. Our study provides a valuable resource for researchers and clinicians to explore prevention and treatment strategies for air-pollution-associated lung cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

Zhang,

Liu,

Wang

et al. 2024

Preprint

View full text Add to dashboard Cite

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Non‐small cell lung cancer with EGFR (L858R and E709X) and CNNB1 mutations responded to afatinib

et al. 2022

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Lung cancer with complex epidermal growth factor receptor (EGFR) and CTNNB1 comutations is rare, and the efficacy of tyrosine kinase inhibitors (TKIs) is generally poor. Here, we encountered a lung cancer patient with complex EGFR (L858R and E709X) and CTNNB1 comutations who successfully responded to afatinib. A 78‐year‐old woman visited our hospital with a cough and bloody sputum that had worsened over the past year. She had multiple mass shadows in both lungs and nodular shadows in the bronchi. The patient was diagnosed with lung adenocarcinoma cT4N3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx target test multi‐CDx system revealed positivity for EGFR (L858R and E709X) and CTNNB1 mutations. The expression of programmed death ligand 1 (22C3 clones) in tumor cells was negative by immunostaining. The patient was treated with afatinib as first‐line therapy and achieved clinical improvement and a partial response and is continuing treatment 1 year later. Case reports of lung cancer patients with EGFR/CTNNB1 comutations are rare, and TKIs are not considered to be effective. We herein present the first case report of lung cancer with the co‐occurrence of uncommon and complex EGFR (L858R and E709X) and CTNNB1 mutations that was successfully treated with afatinib.

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Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

Zhang,

Liu,

Wang

et al. 2024

eLife

View full text Add to dashboard Cite

Air pollution significantly impact lung cancer progression, but there is a lack of a comprehensive molecular characterization of clinical samples associated with air pollution. Here, we performed a proteogenomic analysis of lung adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke is the primary contributor to the high lung cancer incidence. Genomic mutation analysis revealed XWLC as a distinct subtype of LUAD separate from cases associated with smoking or endogenous factors. Mutational signature analysis suggested that Benzo[a]pyrene (BaP) is the major risk factor in XWLC. The BaP-induced mutation hotspot, EGFR-G719X, was present in 20% of XWLC which endowed XWLC with elevated MAPK pathway activations and worse outcomes compared to common EGFR mutations. Multi-omics clustering of XWLC identified four clinically relevant subtypes. These subgroups exhibited distinct features in biological processes, genetic alterations, metabolism demands, immune landscape, tumor microbiota composition and radiomic features. Finally, MAD1 and TPRN were identified as novel potential therapeutic targets in XWLC. Our study provides a valuable resource for researchers and clinicians to explore prevention and treatment strategies for air-pollution-associated lung cancers.

show abstract

Non‐small cell lung cancer with EGFR (L858R and E709X) and CNNB1 mutations responded to afatinib

Cited by 4 publications

References 21 publications

Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

Non‐small cell lung cancer with EGFR (L858R and E709X) and CNNB1 mutations responded to afatinib

Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

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