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  • 1
    Online Resource
    Online Resource
    Real-world large-scale study of ERBB2 gene fusions and its response to afatinib in Chinese non-small cell lung cancer (NSCLC): A multicenter study.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13002-e13002
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13002-e13002
    Abstract: e13002 Background: ERBB2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers (NSCLC) and ERBB2-directed therapies have shown promising results in this unique population, while little is known about ERBB2 fusion association with outcomes of afatinib. The aim of this study was to investigate the efficacy of afatinib in patients with advanced ERBB2 fusion NSCLC. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. To determine the frequency of the ERBB2 fusions in NSCLC and other tumors, we analyzed data from 2743 clinical NSCLC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, eight (0.29%) patients were identified with an ERBB2 fusion, including TNS4-ERBB2 (1), ERBB2-CD79B (1), IGFBP4-ERBB2 (1), ERBB2-PSMD3 (1), SEZ6-ERBB2 (1), ERBB2-PGAP3 (1), ARL5C-ERBB2 (1) and B3GNTL1-ERBB2 (1). The genes most frequently co-altered in patients with ERBB2 fusions were TP53 (37.50%), CDKN2A (25.00%), RB1 (25.00%) and RBM10 (25.00%). Overall TMB in the ERBB2 fusions was low (median 2.97 mut/Mb). For treatments, 25.00% patients chose afatinib, another patients chose chemotherapy or chemoradiotherapy, and case examples of advanced ERBB2 fusion driven NSCLC patients responding to afatinib were actively being sought thru our database. Conclusions: Patients with advanced ERBB2 fusion NSCLC showed a good outcome of afatinib compared to those with ALK/ ROS1 fusion which response to crizotinib, which strengthen the need for effective ERBB2-targeted drugs in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13002
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Incidence of FGFR-TACC gene fusions in Chinese non-small cell lung cancer (NSCLC): A multicenter study.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13001-e13001
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13001-e13001
    Abstract: e13001 Background: Fibroblast growth factor receptors (FGFR) are transmembrane kinase proteins with growing importance in non-small cell lung cancer (NSCLC) biology given the frequency of molecular alterations and vast interface with multiple other signaling pathways. Furthermore, numerous FGFR inhibitors in clinical development demonstrate the expanding therapeutic relevance of this pathway. The aim of this study was to evaluate the prevalence of FGFR-TACC fusions in Chinese NSCLC populations, which had not been reported earlier, and to describe targeting potential in Chinese NSCLC populations. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. Capture-based comprehensive genomic profiling was performed on 2743 NSCLC FFPE samples sequenced to a mean coverage depth of 〉 650X for up to 381 cancer-related genes. Genomic alterations (GA) included short variant (SV) base subs and insertions/deletions, copy number alterations, and rearrangements/fusions. Tumor mutational burden (TMB; mut/Mb) was calculated on up to 1.2 Mb of sequenced DNA. Results: Of this entire cohort, just 16 (0.58%) patients were identified with FGFR-TACC fusions, including FGFR1-TACC 1 fusion (1), FGFR2-TACC2 fusion (3) and FGFR3-TACC3 fusion (12). Median patient age was 57 (range 36-84 years). Of the FGFR-TACC fusion NSCLC patients, 56.25% were detected in female patients. Biopsies were obtained from primary lung tumor (31.25%) and metastatic sites (68.75%). Overall TMB in the FGFR-TACC fusion was low (median 3.6 mut/Mb), although two cases (12.50%) had 〉 20 mut/Mb. Of the FGFR-TACC fusion NSCLC patients, two cases (12.50%) featured EGFR SV alterations. Conclusions: FGFR-TACC fusions occur in a subset of patients with NSCLC. Such patients should be considered for clinical trials featuring FGFR inhibitors (AZD4547). Moreover, NGS can provide information for targeted therapy. For NSCLC patients to benefit from more personalized cancer treatment, clinical therapy should improve with clinical diagnostics through multi-gene assays to determine the actual clinical benefits.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13001
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 3 ( 2023-01-17)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 3 ( 2023-01-17)
    Abstract: The process of oncogene-induced senescence (OIS) and the conversion between OIS and malignant transformation during carcinogenesis is poorly understood. Here, we show that following overactivation of oncogene Ras in lung epithelial cells, high-level transforming growth factor β1 (TGF-β1)–activated SMAD3, but not SMAD2 or SMAD4, plays a determinant role in inducing cellular senescence independent of the p53/p16/p15 senescence pathways. Importantly, SMAD3 binds a potential tumor suppressor ATOH8 to form a transcriptional complex that directly represses a series of cell cycle–promoting genes and consequently causes senescence in lung epithelial cells. Interestingly, the prosenescent SMAD3 converts to being oncogenic and essentially facilitates oncogenic Ras-driven malignant transformation. Furthermore, depleting Atoh8 rapidly accelerates oncogenic Ras-driven lung tumorigenesis, and lung cancers driven by mutant Ras and Atoh8 loss, but not by mutant Ras only, are sensitive to treatment of a specific SMAD3 inhibitor. Moreover, hypermethylation of the ATOH8 gene can be found in approximately 12% of clinical lung cancer cases. Together, our findings demonstrate not only epithelial cellular senescence directed by a potential tumor suppressor–controlled transcriptional program but also an important interplay between the prosenescent and transforming effects of TGF-β/SMAD3, potentially laying a foundation for developing early detection and anticancer strategies.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2208927120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Expert consensus on the diagnosis and treatment of NTRK gene fusion solid tumors in China
    Wiley ; 2022
    In:  Thoracic Cancer Vol. 13, No. 21 ( 2022-11), p. 3084-3097
    Details
    In: Thoracic Cancer, Wiley, Vol. 13, No. 21 ( 2022-11), p. 3084-3097
    Abstract: Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase ( NTRK ) gene fusions are among the first “tumor agnostic” drugs approved for pan‐cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second‐generation drugs designed to overcome first‐generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and (DNA and/or RNA‐based) next‐generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first‐ and second‐generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v13.21
    DOI: 10.1111/1759-7714.14644
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2559245-2
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  • 5
    Online Resource
    Online Resource
    Real-world fusion landscape in advanced Chinese gastric cancer using next generation sequencing: A multicenter study.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 4_suppl ( 2019-02-01), p. 51-51
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 51-51
    Abstract: 51 Background: Gastric cancer (GC) is a highly heterogeneous disease. Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced GC patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. The aim of this study is to investigate fusion landscape in advanced GC. Methods: A multicenter study in China was initiated from Aug. 2016, and GC patients have been enrolled as of Aug. 2018. To determine the fusion frequency in GC, we analyzed data from 371clinical GC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, 61 patients (16.44%) were identified with fusions, including TMEM45B-FGF3 (3), AXIN1-SMPD3 (3), B3GNTL1-ERBB2 (2), ERBB2-LAMA3 (2), ERBB2-ACLY (2), TRIM24-BRAF (2), ARHGEF1-CD79A (2), FGFR4-UIMC1 (2), MSH2-TTC7A (2), SMARCA4-LDLR (2), GON4L-RIT1 (2), AKT1-CPSF2 (2), GATA6-COLEC12 (2), RICTOR-EFNA5 (2), KAT6A-PLAT (2), ROCK1-CCDC178 (2), HBS1L-MYB (2), SLC30A2-ARID1A (2), MSI2-BIRC5 (2), NOTCH3-UCA1 (2), PIK3C2B-KISS1 (2), RICTOR-OSMR (2), FGFR2-MIR5694 (2), FGFR2-FGFR1 (2), MAN2A2-BLM (2), EGFR-MED15 (1), EML4-ALK(1), GOPC-ROS1 (1), FXR2-TP53 (1), NF1-PSMD11 (1), IRS2-PRKCI (1), FGFR2-KIAA1217(1), FGFR2-TACC2 (1), FGFR3-TACC3 (1). ERBB2, BRAF, EGFR, ALK and ROS1 fusionswere seen in 18.03% (11/61) of advanced Chinese gastric cancer fusion landscape patients. Conclusions: Advanced Chinese gastric cancer fusion landscape is rich, ERBB2, BRAF, EGFR, ALK and ROS1 fusions are rare but potentially druggable in TKIs. Detection of ERBB2, BRAF, EGFR, ALK and ROS1 fusions should be part of comprehensive profiling panels to determine TKIs and direct appropriate combination therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.4_suppl.51
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    New first-line treatment strategies for advanced lung squamous cell carcinoma
    AME Publishing Company ; 2020
    In:  Translational Lung Cancer Research Vol. 9, No. 2 ( 2020-4), p. 414-417
    Details
    In: Translational Lung Cancer Research, AME Publishing Company, Vol. 9, No. 2 ( 2020-4), p. 414-417
    Type of Medium: Online Resource
    ISSN: 2218-6751 , 2226-4477
    URL: Journal
    URL: Article
    DOI: 10.21037/tlcr
    DOI: 10.21037/tlcr.2020.03.14
    Language: Unknown
    Publisher: AME Publishing Company
    Publication Date: 2020
    detail.hit.zdb_id: 2754335-3
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  • 7
    Online Resource
    Online Resource
    An EGFR extracellular domain mutation data in the East Asian non-small cell lung cancer populations and response to icotinib: A multicenter study.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13000-e13000
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13000-e13000
    Abstract: e13000 Background: “Pan-negative” non-small cell lung cancer (NSCLC) patient specimens that lack mutations in known targetable genes. EGFR extracellular domain mutations (ECD) as novel oncogenic mutations are found in colorectal cancer, glioma, and neuroblastoma cases and has not yet reported in NSCLC. No enough evidence between icotinib treatment and ECD has been reported in NSCLC. Methods: Comprehensive mutational analyses were performed on 3279 NSCLC specimens. In this cohort of patients, common lung cancer oncogenic driver mutations were firstly detected in EGFR, as well as the KRAS, BRAF, ALK, ROS1 and RET genes by next generation sequencing tumor DNA (ctDNA) and apply icotinib for treatment for EGFR ECD. Results: Of this entire cohort, sixteen (0.49%) patients (3279 cases) were identified with EGFR ECD, including p.L62R (2), p.R98Q (1), p.I213M (1), p.A237F (1), p.A289V (1), p.A289T (1), p.T302H (1), p.T354K (1), p.T363N (1), p.D368Y (1), p.T430S (1), p.A508V (1), p.N528D (1), p.K593Q (1) and G598V (1). During the treatment by icotinib, two cases (p.A289V, p.A289T) had partial response to icotinib for four and six months, which suggested that icotinib conferred sensitivity to A289X mutation. EGFR A289X mutations were sensitive to icotinib treatment in BaF3 cell lines and in xenograft models. These results paralleled those seen with the well-described EGFR oncogenic driver mutation, L858R, suggesting similar mechanistic underpinnings for the mutations. Conclusions: Here, a new EGFR driver mutation, A289X, was identified in the ECD of two NSCLC specimens. NGS may expand the EGFR mutations spectrum for icotinib treatment in NSCLC, however, it needs to be confirmed in more patients with NSCLC in East Asian and other populations.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13000
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Online Resource
    PKMYT1 inhibits lung adenocarcinoma progression by abrogating AKT1 activity
    Springer Science and Business Media LLC ; 2023
    In:  Cellular Oncology Vol. 46, No. 1 ( 2023-02), p. 195-209
    Details
    In: Cellular Oncology, Springer Science and Business Media LLC, Vol. 46, No. 1 ( 2023-02), p. 195-209
    Type of Medium: Online Resource
    ISSN: 2211-3428 , 2211-3436
    URL: Article
    DOI: 10.1007/s13402-022-00744-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2595105-1
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  • 9
    Online Resource
    Online Resource
    Chinese expert consensus on the multidisciplinary management of pneumonitis associated with immune checkpoint inhibitor
    Wiley ; 2022
    In:  Thoracic Cancer Vol. 13, No. 23 ( 2022-12), p. 3420-3430
    Details
    In: Thoracic Cancer, Wiley, Vol. 13, No. 23 ( 2022-12), p. 3420-3430
    Abstract: Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in‐depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v13.23
    DOI: 10.1111/1759-7714.14693
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2559245-2
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  • 10
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    An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness
    Springer Science and Business Media LLC ; 2021
    In:  Nature Communications Vol. 12, No. 1 ( 2021-05-11)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-05-11)
    Abstract: Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-021-22971-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2553671-0
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