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ESMO Open 2021 Jun 18;6(4):100191. Epub 2021 Jun 18.

Department of Thoracic and Breast Surgery, Oita University, Oita, Japan.

Background: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting.

Patients And Methods: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Read More

Hum Pathol 2021 Jun 18. Epub 2021 Jun 18.

Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark; Institute of Pathology, Aarhus University Hospital, 8200 Aarhus N, Denmark.

Aims: The aim of the study was to investigate the advantage of implementing next generation sequencing (NGS) compared with quantitative polymerase chain reaction (qPCR) when performing routine molecular diagnostics in adenocarcinomas of the lung.

Methods: The study is a retrospective cross-sectional observational study of 1839 cytological and histological adenocarcinoma biopsies investigated for gene mutations from 2016 to 2018 at the Department of Pathology at Aarhus University Hospital. A total of 1169 samples were analysed by qPCR for the presence of EGFR hotspot mutations from 2016 to 2017. Read More

Cancer Med 2021 Jun 21. Epub 2021 Jun 21.

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Background: Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a member of B7 family, which is upregulated in multiple tumors. However, its exact functions in non-small cell lung cancer (NSCLC) have not been fully understood. This study aimed to investigate the biological roles of HHLA2 in human NSCLC and the relevant mechanisms. Read More

JCO Precis Oncol 2021 Jan 1;5:325-332. Epub 2021 Feb 1.

Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.

For patients with surgically resected disease, multiple studies suggest a benefit of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in delaying cancer recurrence. The necessary duration of therapy for benefit is unknown.

Materials And Methods: This randomized phase II study enrolled patients with completely resected stage IA-IIIB -mutant non-small-cell lung cancer (American Joint Committee on Cancer 7th edition) after stage-appropriate standard-of-care adjuvant therapy. Read More

Am J Transl Res 2021 15;13(5):4900-4907. Epub 2021 May 15.

Department of Oncology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) Haikou 570311, China.

Objective: This research explored and analyzed LncRNA GAS5 expression in non-small cell lung cancer (NSCLC) tissues and its correlation with Ki67 and EGFR.

Methods: A total of 130 samples of paraffin-embedded NSCLC tissues and para-cancerous normal tissues that were collected in the Department of Pathology from January 2014 to April 2016 were selected. The relative expression of LncRNA GAS5 and Ki67/EGFR in both NSCLC tissues and para-cancerous normal tissues were detected via RT-PCR and immunohistochemistry respectively. Read More

Oncol Lett 2021 Aug 7;22(2):594. Epub 2021 Jun 7.

Department of Immunology, Chengde Medical University, Chengde, Hebei 067000, P.R. China.

Although targeted therapy has emerged as an effective treatment strategy for non-small cell lung cancer (NSCLC), some patients cannot benefit from such therapy due to the limited number of therapeutic targets. The present study aimed to identify mutated genes associated with clinicopathological characteristics and prognosis and to screen for mutations that are not concurrent with applicable drug target sites in patients with NSCLC. Tumor tissue and blood samples were obtained from 97 patients with NSCLC. Read More

Front Pharmacol 2021 3;12:639016. Epub 2021 Jun 3.

Department of Pharmacy, The First Hospital of China Medical University, Shenyang, China.

Resistance to anticancer agents ensures a poor prognosis in patients with lung cancer. Metformin could enhance the anticancer effects of standard antineoplastic agents [traditional chemotherapy drugs, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), or immune checkpoint inhibitors (ICIs)]; however, it is unclear whether metformin can be combined with antineoplastic agents in the treatment of lung cancer. To explore the efficacy of combinational strategies, we performed a systematic review and meta-analysis for diabetic and non-diabetic patients with lung cancer. Read More

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 May;46(5):545-551

Department of Pharmacology, School of Pharmacy, Bengbu Medical College; Anhui Provincial Biochemical Drugs Engineering Technology Research Center, Bengbu Anhui 233030, China.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) can effectively inhibit the growth of EGFR-dependent mutant non-small cell lung cancer (NSCLC). Unfortunately, NSCLC patients often develop severe drug resistance after long-term EGFR-TKI treatment. Studies have shown that the disorder of energy metabolism in tumor cells can induce EGFR-TKI resistance. Read More

Cancer Sci 2021 Jun 19. Epub 2021 Jun 19.

Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan, 920-0934.

Leptomeningeal carcinomatosis (LMC) occurs frequently in non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and is associated with acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, the mechanism by which LMC acquires resistance to osimertinib, a third-generation EGFR-TKI, is unclear. In this study, we elucidated the resistance mechanism and searched for a novel therapeutic strategy. Read More

Cancer Sci 2021 Jun 19. Epub 2021 Jun 19.

Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University, Kanazawa City, Ishikawa, 920-1192, Japan.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, due to acquired resistance to EGFR-TKIs, even patients on third-generation osimertinib, have a poor prognosis. Resistance mechanisms are still not fully understood. Read More

Cancer Sci 2021 Jun 18. Epub 2021 Jun 18.

Devision of Thoracic Surgery, Yokohama City University Medical Center Hospital.

There could be two carcinogenetic pathways for lung adenocarcinoma (LADC), that are, the non-smokers' pathway and the smokers' pathway. This review article describes the two pathways with special reference to potential relationships between histological subtypes, malignant grades, and driver mutations. The lung is composed of two different tissue units, the terminal respiratory unit (TRU) and the central airway compartment (CAC). Read More

iScience 2021 Jun 7;24(6):102522. Epub 2021 May 7.

Institute of Information Science, Academia Sinica, Taipei, 115, Taiwan.

Lung adenocarcinoma (LUAD) patients in East Asia predominantly harbor oncogenic mutations. However, there remains a limited understanding of the biological characteristics and therapeutic vulnerabilities of the concurrent mutations of and other genes in LUAD. Here, we performed comprehensive bioinformatics analyses on 88 treatment-naïve East Asian LUAD patients. Read More

Toxicol Res (Camb) 2021 May 3;10(3):476-486. Epub 2021 May 3.

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.

The epidermal growth factor receptor (EGFR) family is a class of receptor tyrosine kinase playing a central role in carcinogenesis and cancer progression. The members of this family, particularly EGFR and human epidermal growth factor receptor 2 (HER2), are the most extensively studied drug targets for malignancy. Today, numerous tyrosine kinase inhibitors targeting EGFR family have been developed to combat non-small-cell lung cancer and breast cancer. Read More

Nat Commun 2021 06 17;12(1):3697. Epub 2021 Jun 17.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Despite the clinical success of the third-generation EGFR inhibitor osimertinib as a first-line treatment of EGFR-mutant non-small cell lung cancer (NSCLC), resistance arises due to the acquisition of EGFR second-site mutations and other mechanisms, which necessitates alternative therapies. Dacomitinib, a pan-HER inhibitor, is approved for first-line treatment and results in different acquired EGFR mutations than osimertinib that mediate on-target resistance. A combination of osimertinib and dacomitinib could therefore induce more durable responses by preventing the emergence of resistance. Read More

Clin Lung Cancer 2021 May 15. Epub 2021 May 15.

Division of Hematology/Oncology, Department of Internal Medicine, UC Davis Comprehensive Cancer Center, University of California, Davis, Sacramento, CA.

Background: Onalespib is a novel heat shock protein 90 inhibitor (HSP90i). Previous preclinical and clinical studies with HSP90i have demonstrated activity in EGFR-mutant non-small cell lung cancer (NSCLC). This study sought to determine the safety and tolerability of onalespib plus erlotinib in EGFR-mutant NSCLC and to evaluate the preliminary efficacy of the combination in epidermal growth factor receptor exon 20 insertion (EGFRex20ins) NSCLC. Read More

Clin Lung Cancer 2021 May 17. Epub 2021 May 17.

Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. Electronic address:

Background: Intrinsic resistance is a major obstacle in treatment of non-small cell lung cancer (NSCLC) patients with an activating mutation in the epidermal growth factor receptor (EGFR). We investigated co-occurring genetic alterations in circulating tumor DNA (ctDNA) as predictive markers of clinical response to first-line erlotinib.

Methods: Pretreatment plasma samples were collected from 76 patients with EGFR-mutated, advanced-stage NSCLC treated with first-line erlotinib. Read More

Gan To Kagaku Ryoho 2021 Jun;48(6):845-847

Dept. of Respiratory Medicine, National Hospital Organisation Tokyo Medical Center.

A 57-year-old female was diagnosed as having advanced lung adenocarcinoma. Combination chemotherapy using cisplatin plus pemetrexed was introduced. However, her disease progressed during the maintenance therapy with pemetrexed. Read More

Gan To Kagaku Ryoho 2021 Jun;48(6):841-843

Dept. of General Thoracic Surgery, Japanese Red Cross Maebashi Hospital.

A 59-year-old man clinically diagnosed with primary lung cancer underwent left lower lobectomy and lymph node dissection( ND2a-2). The postoperative pathological stage was ⅠB(pT2aN0M0), and the lesion was positive for epidermal growth factor receptor(EGFR)exon 21 L858R mutation. Thirty months after surgery, the patient developed pleural dissemination and effusion in the left pleural cavity. Read More

Gan To Kagaku Ryoho 2021 Jun;48(6):837-839

Dept. of Hospital Pharmacy, Fukuoka University Hospital.

A man in his 40s underwent a transbronchial lung biopsy and received a diagnosis of adenocarcinoma of the right upper lobe of the lung(cT4N0M0, Stage Ⅲ)with no EGFR gene mutation, no ALK fusion gene, no ROS1 fusion gene, and a tumor proportion score(TPS)of 50-74%. During the postoperative follow-up period, enlarged right supraclavicular lymph nodes and right upper and lower paratracheal lymph nodes were detected, diagnosed as recurrence by positron emission tomography-computed tomography. Although a positive rheumatoid factor test, as the patient had no symptoms of rheumatoid arthritis(RA), treatment with pembrolizumab was initiated. Read More

Ann Oncol 2021 Jun 14. Epub 2021 Jun 14.

Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan. Electronic address:

Background: This international, randomized, double-blind phase III study (ONO-4538-52/TASUKI-52) evaluated nivolumab with bevacizumab and cytotoxic chemotherapy as first-line treatment for non-squamous non-small cell lung cancer (NSCLC).

Patients And Methods: Between June 2017 and July 2019, this study enrolled treatment-naïve patients with stage IIIB/IV or recurrent non-squamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. They were randomly assigned in a 1:1 ratio to receive nivolumab or placebo in combination with carboplatin, paclitaxel, and bevacizumab every 3 weeks for up to 6 cycles, followed by nivolumab/placebo with bevacizumab until progressive disease or unacceptable toxicity. Read More

J Med Chem 2021 Jun 17. Epub 2021 Jun 17.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.

Proteolysis-targeting chimera (PROTAC) is an attractive technology in drug discovery. Canonically, targets act as a basic starting point in the most previous PROTAC design. Here, we designed degraders considering from the view of clinical benefits. Read More

Acta Oncol 2021 Jun 17:1-6. Epub 2021 Jun 17.

Department of Medical Oncology and Radiotherapy and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.

Background: With the first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), clinical benefit and rash correlate together. EGFR TKI-induced rash can be alleviated with topical corticosteroids and tetracyclines. This study investigates whether prophylaxis with topical corticosteroids is associated with improved survival among the EGFR TKI-treated non-small cell lung cancers (NSCLCs). Read More

Front Oncol 2021 31;11:630672. Epub 2021 May 31.

Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, China.

Background: Lung cancer is a malignant tumor that has the highest morbidity and mortality rate among all cancers. Early diagnosis of lung cancer is a key factor in reducing mortality and improving prognosis.

Methods: In this study, we performed CTC next-generation sequencing (NGS) in early-stage lung cancer patients to identify lung cancer-related gene mutations. Read More

Front Oncol 2021 31;11:591922. Epub 2021 May 31.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Clinical evidence has shown that few non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor () mutations can benefit from immunotherapy. The tumor immune microenvironment (TIME) is a significant factor affecting the efficacy of immunotherapy. However, the TIME transformational process in -mutation patients is unknown. Read More

Zhongguo Fei Ai Za Zhi 2021 Jun 17. Epub 2021 Jun 17.

Department of Stereotactic Radiotherapy, Qingdao Central Hospital, Qingdao 266042, China.

Background: Immune checkpoint inhibitor associated pneumonia (CIP) is a serious side effect of immune checkpoint inhibitors. There is a consensus on the treatment of acute phase of CIP, but the treatment of pulmonary interstitial fibrosis after the acute phase is still a clinical problem to be solved.

Methods: The diagnosis and treatment of a non-small cell lung cancer (NSCLC) patient with immune checkpoint inhibitor associated pneumonia in the Stereotactic Radiotherapy Department of Qingdao Central Hospital were retrospectively analyzed, and literatures were reviewed. Read More

Clin Lung Cancer 2021 May 16. Epub 2021 May 16.

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. Electronic address:

Background: Epidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20-ins) mutations are an uncommon and heterogeneous group of non-small cell lung cancers (NSCLCs), resistant to conventional EGFR tyrosine kinase inhibitors (TKIs). Characteristics and outcomes of patients with EGFR ex20-ins have not been fully established; we sought to clarify them using a multinational patient database.

Patients And Methods: Patients with NSCLC from six Australian institutions with EGFR exon 20 mutations (ex20-mut), excluding T790M, were retrospectively reviewed. Read More

Lung Cancer 2021 Feb 27;158:74-84. Epub 2021 Feb 27.

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China; State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

Objective: To compare the efficacy and safety of treatment modalities across different populations with non-small cell lung cancer and brain metastases.

Methods: A comprehensive search for randomized controlled trials was conducted in databases including PubMed, Embase, the Cochrane library, the ClinicalTrials.gov, and major international conferences. Read More

Cancer Immunol Immunother 2021 Jun 14. Epub 2021 Jun 14.

Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, Heidelberg, Germany.

Introduction: The advent of immune checkpoint blockade (ICB) has led to significantly improved disease outcome in lung adenocarcinoma (ADC), but response of ALK/EGFR-positive tumors to immune therapy is limited. The underlying immune biology is incompletely understood.

Methods: We performed comparative mRNA expression profiling of 31 ALK-positive, 40 EGFR-positive and 43 ALK/EGFR-negative lung ADC focused on immune gene expression. Read More

Front Oncol 2021 28;11:659065. Epub 2021 May 28.

Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China.

Objective: To explore the efficacy and safety of EGFR-TKI combined with thymosin therapy in advanced non-small cell lung cancer (NSCLC) patients harboring active EGFR mutations.

Methods: Patients confirmed as advanced NSCLC with active EGFR mutations were recruited from August 2008 to July 2018 retrospectively. Patients treated with EGFR-TKI were classified as the EGFR-TKI group. Read More

Dis Markers 2021 27;2021:5530673. Epub 2021 Apr 27.

Research Department, GuangXi Medical University Cancer Hospital, Nanning, Guangxi, China.

. Despite afatinib as a new first-line treatment for EGFR L858R and exon 19 deletion or other rare EGFR-mutation patients, the acquired resistance or toxic effects associated with it limited its use clinically. The controlling of acquired resistance or optimization of the afatinib dosage in EGFR/T790M mutation-positive non-small-cell lung cancer (NSCLC) is still an important fundamental problem. Read More