Afatinib combined with anlotinib in the treatment of lung adenocarcinoma patient with novel HER2 mutation: a case report and review of the literature

Abstract Background HER2 is a member of the ERBB family of receptor tyrosine kinases, and HER2 mutations occur in 1–4% of non-small cell lung cancer (NSCLC) as an oncogenic driver mutation. We found a rare mutation of HER2 p.Asp769Tyr in NSCLC. Case presentation We presented a case of a 68-year-old nonsmoking male patient with brain metastasis from lung adenocarcinoma harboring a rare mutation of HER2 p.Asp769Tyr. After multiple lines of treatment, he obtained a durable response (10 months) to afatinib and anlotinib. Conclusion We reported for the first time that afatinib and anlotinib have successfully treated lung adenocarcinoma with HER2 p.Asp769Tyr mutation. This finding can provide an insight into the optimal treatment of lung adenocarcinoma patients with novel mutations. Additionally, we summarized the efficacy of targeted therapy for HER2 mutant lung cancer in this article.

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Requirement for PKC Epsilon in Kras-Driven Lung Tumorigenesis

10.1101/2020.06.26.173690 ◽

2020 ◽

Author(s):

Rachana Garg ◽

Mariana Cooke ◽

Shaofei Wang ◽

Fernando Benavides ◽

Martin C. Abba ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cancer Therapeutics ◽

Rna Seq ◽

Lung Tumorigenesis ◽

Mechanistic Analysis ◽

Oncogenic Driver ◽

Histological Form

ABSTRACTNon-small cell lung cancer (NSCLC), the most frequent subtype of lung cancer, remains a highly lethal malignancy and one of the leading causes of cancer deaths worldwide. Mutant KRAS is the prevailing oncogenic driver of lung adenocarcinoma, the most common histological form of NSCLC. In this study, we examined the role of PKCε, an oncogenic kinase highly expressed in NSCLC and other cancers, in KRAS-driven tumorigenesis. Notably, database analysis revealed an association between PKCε expression and poor outcome in lung adenocarcinoma patients specifically having KRAS mutation. By generating a PKCε-deficient, conditionally activatable allele of oncogenic Kras (LSL-KrasG12D;PKCε−/− mice) we were able to demonstrate the requirement of PKCε for Kras-driven lung tumorigenesis in vivo, which is consistent with the impaired transformed growth observed in PKCε-deficient KRAS-dependent NSCLC cells. Moreover, PKCε-knockout mice were found to be less susceptible to lung tumorigenesis induced by benzo[a]pyrene, a carcinogen that induces mutations in Kras. Mechanistic analysis using RNA-Seq revealed little overlapping for PKCε and KRAS in the control of genes/biological pathways relevant in NSCLC, suggesting that a permissive role of PKCε in KRAS-driven lung tumorigenesis may involve non-redundant mechanisms. Our results thus highlight the relevance and potential of targeting PKCε for lung cancer therapeutics.

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Durable Response to the Combination of Atezolizumab With Platinum-Based Chemotherapy in an Untreated Non-Smoking Lung Adenocarcinoma Patient With BRAF V600E Mutation: A Case Report

Frontiers in Oncology ◽

10.3389/fonc.2021.634920 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaomin Niu ◽

Yingjia Sun ◽

David Planchard ◽

Luting Chiu ◽

Jian Bai ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Nsclc Patient ◽

Braf Inhibitor ◽

Progression Free Survival ◽

Braf V600e ◽

First Line ◽

Liquid Biopsies ◽

Durable Response ◽

Platinum Based Chemotherapy ◽

Lung Adenocarcinoma Patient

BackgroundImmune checkpoint inhibitor (ICPi) has become a major treatment in advanced non-small cell lung cancer (NSCLC) and demonstrated a clinical benefit for NSCLC patients with high programmed death ligand-1 (PD-L1) expression without EGFR/ALK/ROS1 drivers; however, the benefit in BRAF V600E NSCLC is so far unknown. Here, we report a case of prolonged tumor response to the combination of immunotherapy with chemotherapy in a non-smoking BRAF V600E NSCLC patient.Materials and MethodsWe verify a co-expression of BRAF V600E mutation and PD-L1 high expression more than 50% on formalin-fixed paraffin-embedded tumor sample of a newly diagnosed lung adenocarcinoma patient by immunohistochemistry and BRAF V600E/EGFR/ALK/ROS1 Mutations Detection Kit. The tissue and liquid biopsies were further subjected to next-generation sequencing (NGS) for identification of mutations with progression on immunotherapy and BRAF inhibitor (BRAFi). The patient had provided written informed consent and authorized the publication of clinical case.ResultsWe demonstrate the case of 62-year-old female non-smoker with high PD-L1 expression and BRAF V600E mutated NSCLC. The progression-free survival (PFS) of first-line combination of atezolizumab with platinum-based chemotherapy and sequential second-line treatment with BRAFi Vemurafenib are 20 and 5.5 months, respectively.ConclusionThis case shows a durable response to ICPi in BRAF V600E non-smoking lung adenocarcinoma with PFS of 20 months under first-line atezolizumab plus chemotherapy treatment. The case supports the idea that the combination immunotherapy may be an attractive option for BRAF V600E mutated non-smoking NSCLC with high PD-L1 expression.

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Role of race in oncogenic driver prevalence and outcomes in lung adenocarcinoma: Results from the Lung Cancer Mutation Consortium

Cancer ◽

10.1002/cncr.29812 ◽

2015 ◽

Vol 122 (5) ◽

pp. 766-772 ◽

Cited By ~ 30

Author(s):

Conor E. Steuer ◽

Madhusmita Behera ◽

Lynne Berry ◽

Sungjin Kim ◽

Michael Rossi ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cancer Mutation ◽

Oncogenic Driver

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17α-Ethynylestradiol and 4-Nonylphenol Stimulate Lung Adenocarcinoma Cells Production in Xenoestrogenic Way

10.20944/preprints201807.0401.v1 ◽

2018 ◽

Author(s):

Chia-Hung Sun ◽

Jou-Chun Chou ◽

Kuan-Po Chao ◽

Hsian-Chi Chang ◽

Fu-Kong Lieu ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Air Pollutants ◽

Estrogenic Activity ◽

Growth Factor Receptor ◽

Adenocarcinoma Cells ◽

Epidermal Growth ◽

Lung Adenocarcinoma Cells ◽

First Time ◽

Female Lung Cancer

Lung cancer has been the leading cause of cancer death in the world. In addition to smoking, estrogen is supposed to play an important role in the lung cancer development because women have a higher proportion of adenocarcinoma than men. In the environment, there are many metabolites and wastes that mimic human estrogen structurally and functionally. As an oral contraceptive, 17α-ethynylestradiol (EE2) is released to wastewater after being utilized. Moreover, 4-nonylphenol (NP) exiting in the petrochemical products and air pollutants has estrogenic activity. In our study, 17β-estradiol (E2), EE2, and NP are administered to stimulate A549 male lung adenocarcinoma cells and H1435 female lung adenocarcinoma cells. The results demonstrate that EE2 and NP stimulate A549 and H1435 cells proliferation in a dose- and time-dependent trend. Both estrogen receptor α and β are activated simultaneously during these processes. Up-regulation of epidermal growth factor receptor (EGFR) and ERK expression is involved in response to estrogens. In conclusion, we first time report that EE2 and NP exert biotoxic effect to stimulate the proliferation of both male and female lung cancer cells in a dose- and time- response manner. New challenges from environmental hormones to lung cancer deserved further investigation.

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ZNF280A Promotes Lung Adenocarcinoma Development through Regulating the Expression of EIF3C

10.21203/rs.3.rs-26101/v1 ◽

2020 ◽

Author(s):

Hongsheng Liu ◽

Yingzhi Qin ◽

Na Zhou ◽

Dongjie Ma ◽

Yingyi Wang

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Small Cell Lung ◽

Normal Tissues ◽

Tumor Promotor ◽

And Migration ◽

First Time ◽

The Relationship

Abstract Background: Lung cancer is the most commonly diagnosed malignant tumor worldwide. Lung adenocarcinoma (LUAD) is the most common histological subtype in non-small cell lung cancer (NSCLC). The relationship between ZNF280A and LUAD has not been demonstrated and remains unclear. Methods: In this study, it was demonstrated that ZNF280A was upregulated in LUAD tissues compared with the normal tissues. Further investigations indicated that the overexpression/knockdown of ZNF280A could promote/inhibit proliferation, colony formation and migration of LUAD cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of ZNF280A could also suppress tumorigenicity of LUAD cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of ZNF280A and identified EIF3C as the potential target. Results: Furthermore, our study revealed that knockdown of EIF3C could inhibit development of LUAD in vitro, and alleviate the ZNF280A overexpression induced promotion of LUAD. Conclusions: In conclusion, our study showed, as the first time, ZNF280A as a tumor promotor for LUAD, whose function was carried out probably through the regulation of EIF3C.

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Molecular biomarkers for lung adenocarcinoma

European Respiratory Journal ◽

10.1183/13993003.01734-2016 ◽

2017 ◽

Vol 49 (4) ◽

pp. 1601734 ◽

Cited By ~ 24

Author(s):

Olivier Calvayrac ◽

Anne Pradines ◽

Elvire Pons ◽

Julien Mazières ◽

Nicolas Guibert

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cell Lung Cancer ◽

Epidemiological Data ◽

Nonsmall Cell Lung Cancer ◽

Therapeutic Strategies ◽

Molecular Biomarkers ◽

Therapeutic Impact ◽

Epidemiological Features ◽

Oncogenic Driver

The identification of oncogenic driver alterations that underlie sensitivity to small inhibitors has led to growing interest in identifying additional targetable oncogenes in nonsmall cell lung cancer. Although the therapeutic impact of the discovery of these alterations has now been widely demonstrated, the epidemiological data associated with each of these biomarkers remain insufficiently studied. In this review, we discuss the techniques used to discover each of these candidate oncogenes, their prevalence in nonsmall cell lung cancer, and briefly outline the epidemiological features of the major oncogenes and ways in which their identification can determine therapeutic strategies.

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EPHA mutation as a predictor of immunotherapeutic efficacy in lung adenocarcinoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001315 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001315

Author(s):

Hua Bai ◽

Jianchun Duan ◽

Chengcheng Li ◽

Wenzhuan Xie ◽

Wenfeng Fang ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cell Lung Cancer ◽

Tyrosine Kinases ◽

Transforming Growth Factor ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

The Cancer Genome Atlas ◽

Mechanism Analysis ◽

Discovery Cohort

BackgroundEphrin type-A receptors (EPHA) are members of family of receptor tyrosine kinases and are related to tumor immunogenicity and immune microenvironment, however, the association between EPHA mutation (EPHAmut) and efficacy of immune checkpoint inhibitors (ICIs) has not been investigated in non-small cell lung cancer (NSCLC).MethodsMultiple cohorts were used to assess the immunotherapeutic predictive performance of EPHAmut, including one discovery cohort (n=79) and two public validation cohort (cohort 1: NSCLC, n=165; cohort 2: pan-cancer, n=1662). The Cancer Genome Atlas cohort was used for prognostic analysis and mechanism exploration.ResultsIn the discovery cohort, patients with EPHAmut had superior disease control rate (72.2% vs 36.1%, p=0.01) and progression-free survival (PFS) (HR 0.38; 95% CI 0.21 to 0.68; p<0.001) compared with those with wide-type EPHA (EPHAwt) in NSCLC. The association between EPHAmut and immunotherapy outcomes in NSCLC was consistently observed in the validation cohorts by multivariable models (cohort 1, PFS HR 0.59; 95% CI 0.37 to 0.96; p=0.03; cohort 2, overall survival (OS) HR 0.63; 95% CI 0.41 to 0.98; p=0.04). Further pooled estimates of the discovery and validation cohorts showed that patients with EPHAmut exhibited a significantly longer PFS and OS in lung adenocarcinoma (LUAD) while not squamous cell lung cancer (LUSC). Consistently, mechanism analysis revealed that patients with EPHAmut was associated with increased T cell signatures and downregulated transforming growth factor-β signaling compared with patients with EPHAwt in LUAD while not LUSC.ConclusionsOur results demonstrated that EPHAmut is an independent classifier that could stratify patients with LUAD for ICIs therapy. Further prospective studies are warranted.Trial registration numberNCC2016JZ-03, NCC2018-092.

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Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience

Journal of Thoracic Oncology ◽

10.1097/jto.0000000000000516 ◽

2015 ◽

Vol 10 (5) ◽

pp. 768-777 ◽

Cited By ~ 172

Author(s):

Lynette M. Sholl ◽

Dara L. Aisner ◽

Marileila Varella-Garcia ◽

Lynne D. Berry ◽

Dora Dias-Santagata ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Mutation Analysis ◽

Driver Mutation ◽

Cancer Mutation ◽

Oncogenic Driver

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Identification of a Rare EGFR T790I Mutation in Lung Adenocarcinoma Sensitive to Osimertinib

Frontiers in Oncology ◽

10.3389/fonc.2021.727312 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yu Wang ◽

Songtao Liu ◽

Alei Feng ◽

Huan Luo ◽

Jinwei Hu ◽

...

Keyword(s):

Lung Cancer ◽

Glomerular Filtration Rate ◽

Lung Adenocarcinoma ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Treatment Strategies ◽

Chinese Patient ◽

T790m Mutation ◽

Rare Mutation

Estimated glomerular filtration rate (EGFR)-sensitive mutations are extremely important for targeted treatment strategies in lung cancer. Osimertinib can effectively inhibit the activity of EGFR-sensitive mutations, including the T790M mutation. However, the efficiency of osimertinib for rare mutation types of T790 is unclear. Here, we report the case of a Chinese patient with lung adenocarcinoma (LADC) harboring a T790I mutation who achieved significant benefits from osimertinib treatment.

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