Genomic characterisation of de novo EGFR copy number gain and its impact on the efficacy of first-line EGFR-tyrosine kinase inhibitors for EGFR mutated non-small cell lung cancer

Xu, Yiquan; Yan, Jingjing; Zhou, Chengzhi; Wu, Lin; Wang, Haibo; Zhao, Jun; Zhou, Min; Wang, Jingyi; Zheng, Xinlong; Zhang, Longfeng; Jiang, Kan; Zheng, Xiaobin; Miao, Qian; Wu, Shiwen; Zou, Zihua; lian, Rong; He, Yuxia; Chen, Rongrong; Yang, Shanshan; Li, Yujing; Chen, Sihui; Lin, Gen

doi:10.1016/j.ejca.2023.04.009

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…Consequently, the patient was diagnosed with right lung adenocarcinoma with pleural metastasis (cT4N0M1a, stage IVa). To identify targetable mutations, the tumor biopsy specimen was sequenced by capture-based next-generation DNA sequencing with a panel containing 73 cancer-related genes ( ( 6 ) gene list is shown in Supplementary Table 1 , Beijing Geneplus Technology Co., Ltd.). The mean effective depth of coverage of the sequence was 2,032×.…”

Section: Case Presentationmentioning

confidence: 99%

Novel PPFIA1-ALK, ALK-C2orf91(intergenic) double-fusion responded well to alectinib in an advanced lung adenocarcinoma patient: a case report

Yan,

Zheng,

Pan

et al. 2023

Front. Oncol.

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Non-small cell lung cancers (NSCLCs) with anaplastic lymphoma kinase (ALK)-rearrangement have favorable responses to ALK inhibitors. However, ALK fusion mutations harbored approximately 90 distinct fusion partners. Patients with different ALK fusions might respond distinctly to different-generation ALK inhibitors. In this case report, we identified a novel non-reciprocal ALK fusion, ALK-C2orf91(intergenic) (A19: intergenic) and PPFIA1-ALK (P2:A20), by next-generation DNA sequencing in an advanced lung adenocarcinoma patient. After 2 months of alectinib, the targeted lung lesion regressed significantly, and evaluation of therapeutic efficiency indicated partial response. To date, the patient had achieved 12 months of progression-free survival from alectinib treatment. Our study extended the spectrum of ALK fusion partners in ALK-positive NSCLC, and we reported a new ALK fusion, PPFIA1-ALK and ALK-C2orf91(intergenic), and its sensitivity to alectinib firstly in lung cancer. We believe that this case report has an important clinical reference.

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Section: Case Presentationmentioning

confidence: 99%

Novel PPFIA1-ALK, ALK-C2orf91(intergenic) double-fusion responded well to alectinib in an advanced lung adenocarcinoma patient: a case report

Yan,

Zheng,

Pan

et al. 2023

Front. Oncol.

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“…In patients with NSCLC harboring EGFRex20ins, approximately 75% exhibit negative expression of programmed death ligand 1 (PD‐L1) and a lower average tumor mutational burden (TMB) of approximately four mutations per megabase. While there have been reports suggesting that TP53 mutations may be related to TKI resistance, the unique genomic profiling of EGFRex20ins and its correlation with treatment efficacy and prognosis and the underlying mechanisms may require further exploration 42–44 …”

Section: Introductionmentioning

confidence: 99%

Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non‐small cell lung cancer

Pan,

Liang,

Shi

et al. 2023

Thoracic Cancer

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The third most prevalent type of epidermal growth factor receptor (EGFR) mutation, EGFR exon 20 insertions (EGFRex20ins), involves 2%–12% of all cases of EGFR‐positive non‐small cell lung cancer (NSCLC). Approximately 90% of the mutations occur within the loop structure region, and the most frequently reported subtypes are A767_V769dup and S768_D770dup, which together account for almost 50% of instances. Apart from the unique subtype of A763_Y764insFQEA, NSCLCs with EGFRex20ins are resistant to approved EGFR tyrosine kinase inhibitors (TKIs) and are also insensitive to chemotherapy or immunotherapy. A new modality of treatment for NSCLC patients with EGFRx20ins has been established with the approval of mobocertinib and amivantamab. There are also numerous novel targeted treatments for NSCLC with EGFRex20ins in development, which are anticipated to improve this patient population's survival even further. This review provides a reference for the clinical management of these patients by summarizing the most recent epidemiological, and clinicopathological characteristics, diagnostic techniques, and therapeutic advances of EGFRex20ins in NSCLC.

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Raddeanin A Improves the Therapeutic Effect of Osimertinib in NSCLC by Accelerating ROS/NLRP3-mediated Pyroptosis

Lin,

Wu,

Jiang

et al. 2023

CPD

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Background: Osimertinib (Osm) is the preferred treatment for non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) T790M mutation. Nevertheless, the resistance of NSCLC cells to Osm will eventually develop, which remains the biggest obstacle to treating such diseases. Raddeanin A (RA) exhibits a potent anti-tumor effect on various types of cancer cells. In this study, we aimed to investigate whether RA suppresses NSCLC growth and increases the therapeutic effect of Osm. background: Osimertinib (Osm) is the preferred treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) T790M mutation. Nevertheless, the resistance of NSCLC cells to Osm will eventually develop, which remains the biggest obstacle to treating such diseases. Raddeanin A (RA) exhibits a potent anti-tumor effect on various types of cancer cells. In the study, we aimed to investigate whether RA suppresses NSCLC growth and synergistically increases the therapeutic effect of Osm. Methods: The effects of RA on inhibiting NSCLC cell viability and proliferation were tested using cell counting kit 8 (CCK-8) and EdU assay. The roles of RA in improving the anti-tumor effect of Osm were tested with CCK-8 and colony formation assays. The roles of RA in regulating reactive oxygen species (ROS)/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3)-mediated pyroptosis were assessed using quantitative real- time PCR (qRT-PCR) and western blotting analysis. objective: N/A Results: RA treatment decreased A549 and H1975 cell viability in a dose- and time-dependent way. RA inhibited NSCLC cell proliferation and tumor growth in vivo. Mechanistically, RA induced ROS overgeneration and resulted in subsequent NLRP3-mediated pyroptosis. In particular, combination treatment with Osm and RA reduced cell viability and clonogenic growth capacity more efficiently than Osm mono treatment in A549 and H1975 cells. Combination treatment also promoted NLRP3-mediated pyroptosis more efficiently than Osm mono treatment. Conclusion: RA inhibited the NSCLC growth and increased the anti-tumor role of Osm in NSCLC by facilitating ROS/NLRP3-mediated pyroptosis. These results suggested that combination therapy with RA and Osm might be an effective strategy to treat Osm-resistant NSCLC. result: N/A other: N/A

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Genomic characterisation of de novo EGFR copy number gain and its impact on the efficacy of first-line EGFR-tyrosine kinase inhibitors for EGFR mutated non-small cell lung cancer

Cited by 3 publications

References 41 publications

Novel PPFIA1-ALK, ALK-C2orf91(intergenic) double-fusion responded well to alectinib in an advanced lung adenocarcinoma patient: a case report

Novel PPFIA1-ALK, ALK-C2orf91(intergenic) double-fusion responded well to alectinib in an advanced lung adenocarcinoma patient: a case report

Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non‐small cell lung cancer

Raddeanin A Improves the Therapeutic Effect of Osimertinib in NSCLC by Accelerating ROS/NLRP3-mediated Pyroptosis

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