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Nat Commun 2022 Jun 28;13(1):3711. Epub 2022 Jun 28.

Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.

Chemotherapy 2022 Jun 28. Epub 2022 Jun 28.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths worldwide. Its medical significance has spurred broad investigations into its treatment and prognosis. Shortly after the oncogenic driver mutations were identified, targeted therapies for NSCLC developed rapidly, including the discovery of tyrosine kinase inhibitors (TKIs). Read More

Int J Cancer 2022 Jun 28. Epub 2022 Jun 28.

Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan (R.O.C.).

High-grade neuroendocrine tumors (NETs) of the lung consist of small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). Both exhibit aggressive malignancy with poor prognosis. The transformation of lung adenocarcinoma (ADC) to SCLC or LCNEC also contributes to acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Read More

Exp Biol Med (Maywood) 2022 Jun 28:15353702221102872. Epub 2022 Jun 28.

Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, China.

Despite significant advances in targeted and immune therapy for non-small cell lung cancer (NSCLC), effective therapies for wild-type epidermal growth factor receptor/anaplastic lymphoma kinase () with low expression of programmed death ligand-1 (PD-L1) NSCLC remain elusive. Numerous studies have shown that ferroptosis plays an essential role in antitumor activity. To identify the molecular regulation patterns associated with ferroptosis, 351 NSCLC samples with low-level PD-L1 were extracted from The Cancer Genome Atlas (TCGA) and clustered using the k-means clustering technique. Read More

J Transl Med 2022 Jun 27;20(1):292. Epub 2022 Jun 27.

Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.

Expert Opin Pharmacother 2022 Jun 27. Epub 2022 Jun 27.

Health Outcomes Division, The University of Texas at Austin, College of Pharmacy, Austin, TX, USA.

Introduction: Although tyrosine kinase inhibitors (TKIs) have improved the efficacy of treatment for non-small cell lung cancer (NSCLC), the accessibility of TKIs is limited due to high costs. Despite the critical role of the cost-effectiveness of TKIs on decision making, no systematic reviews have compared the cost-effectiveness of comparable TKIs. Therefore, we systemically reviewed the economic evaluation studies on various TKIs for NSCLC. Read More

J Clin Oncol 2022 Jun 27:JCO2201136. Epub 2022 Jun 27.

Departments of Internal Medicine and Pharmacology, Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX.

Front Oncol 2022 8;12:902967. Epub 2022 Jun 8.

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Among the several next-generation tyrosine kinase inhibitors (TKIs) tested against uncommon EFGR alterations, poziotinib has been demonstrated to be a powerful agent for metastatic non-small-cell lung cancer (mNSCLC) with aberrations in exon 20, and FDA approval is being sought in the previously-treated population. Poziotinib has also shown activity in mNSCLC with aberrations in EGFR exon 20. Herein, we report the first published case of a patient affected by mNSCLC harbouring an exon 20 insertion (EGFRex20ins) mutation who achieved a complete response (CR) under treatment with poziotinib as part of the ZENITH20 trial. Read More

Front Oncol 2022 8;12:876051. Epub 2022 Jun 8.

Thoracic Medicine Research Center, Taipei Medical University, Taipei, Taiwan.

Objective: Platelet activation and adhesion to cancer cells increase the release of multiple factors that contribute to EMT and chemoresistance. Elevated levels of D-dimer have been associated with poor clinical outcomes in lung cancer. Platelets in high D-dimer plasma may be activated and implicated in acquired resistance to EGFR TKI in advanced lung adenocarcinoma with mutant EGFR. Read More

RSC Adv 2022 Jun 7;12(26):16779-16789. Epub 2022 Jun 7.

School of Biochemical Engineering, Indian Institute of Technology (BHU) Uttar Pradesh Varanasi 221 005 India.

Double mutated epidermal growth factor receptor is a clinically important target for addressing drug resistance in lung cancer treatment. Therefore, discovering new inhibitors against the T790M/L858R (TMLR) resistant mutation is ongoing globally. In the present study, nearly 150 000 molecules from various natural product libraries were screened by employing different ligand and structure-based techniques. Read More

Clin Lung Cancer 2022 Jun 3. Epub 2022 Jun 3.

Department of Medicine, Stanford University School of Medicine, Stanford, CA; Division of Oncology, Stanford University School of Medicine, Stanford, CA; Stanford Cancer Institute, Stanford, CA. Electronic address:

Introduction: About 3%-5% of mNSCLC have ERBB2 (HER2) alterations, but currently, there are no FDA-approved targeted therapies for this indication. We compared treatment response between trastuzumab-based and non-targeted regimens in ERBB2-mutant mNSCLC.

Methods: This retrospective, single-institution study included patients with mNSCLC with ERBB2 alterations identified by next-generation sequencing. Read More

J Transl Med 2022 Jun 25;20(1):286. Epub 2022 Jun 25.

Department of Experimental Medicine, University of Rome "Sapienza", viale Regina Elena 324, 00161, Rome, Italy.

Malignant mesothelioma (MM) is a rare orphan aggressive neoplasia with low survival rates. Among the other signaling pathways, ErbB receptors and Hh signaling are deregulated in MM. Thus, molecules involved in these signaling pathways could be used for targeted therapy approaches. Read More

Per Med 2022 Jun 24. Epub 2022 Jun 24.

Thoracic Tumors Unit, Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, 08036, Spain.

In recent years, major advances have been achieved in our understanding of non-small-cell lung cancer (NSCLC) with oncogenic driver alterations and in the specific treatment of these with tyrosine kinase inhibitors. Currently, state-of-the-art management of patients with NSCLC (particularly adenocarcinoma or non-adenocarcinoma but with mild tobacco exposure) consists of the determination of , ,  and status, as they have US FDA and EMA approved targeted therapies. The increase in molecular knowledge of NSCLC and the development of drugs against other targets has settled new therapeutic indications. Read More

FEBS Open Bio 2022 Jun 23. Epub 2022 Jun 23.

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Tumor necrosis factor receptor-associated factor 4 (TRAF4) is overexpressed in a variety of carcinomas of different origins, but its role in tumorigenesis remains incompletely understood. Previous studies suggest that TRAF4 promotes EGFR activation in non-small cell lung cancer (NSCLC). However, the downstream signaling pathway of TRAF4-mediated EGFR activation, as well as its effects on tumor cells, have not been fully elucidated. Read More

Cancer Med 2022 Jun 23. Epub 2022 Jun 23.

Upstate Cancer Center, Upstate Medical University, Syracuse, New York, USA.

Introduction: New treatment strategies for advanced non-small-cell lung carcinoma (NSCLC) include synthetic lethality targets focused on protein arginine methyl transferases such as PRMT5 that exploit the impact of genomic loss of methylthioadenosine phosphorylase (MTAP).

Methods: Twenty nine thousand three hundred seventy nine advanced NSCLC cases underwent hybrid-capture based comprehensive genomic profiling between June 1, 2018 and May 31, 2020. PD-L1 expression was determined by immunohistochemistry (Dako 22C3 PharmDx assay). Read More

Zhongguo Fei Ai Za Zhi 2022 Jun;25(6):409-419

Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, 
West China Hospital, Sichuan University, Chengdu 610041, China.

Background: The incidence of symptomatic radiation pneumonitis (RP) and its relationship with dose-volume histogram (DVH) parameters in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and concurrent once-daily thoracic radiotherapy (TRT) remain unclear. We aim to analyze the values of clinical factors and dose-volume histogram (DVH) parameters to predict the risk for symptomatic RP in these patients.

Methods: Between 2011 and 2019, we retrospectively analyzed and identified 85 patients who had received EGFR-TKIs and once-daily TRT simultaneously (EGFR-TKIs group) and 129 patients who had received concurrent chemoradiotherapy (CCRT group). Read More

Front Oncol 2022 7;12:805538. Epub 2022 Jun 7.

Department of Thoracic Oncology of Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

EGFR-TKI is widely used for EGFR-mutant NSCLC patients. Bleeding is reported as a neglected adverse effect induced by EGFR-TKI. Female patients with lung adenocarcinoma have a high frequency of EGFR mutations. Read More

Pharmaceutics 2022 Jun 5;14(6). Epub 2022 Jun 5.

Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

Pancreatic cancer is one of the most common causes of death in Taiwan. Previous studies have shown that more than 90% of pancreatic cancer cells presented epidermal growth factor receptor (EGFR) cell marker, and this marker is thought to be important as it is related to activation of cancer cell proliferation, angiogenesis, and cancer progression. Moreover, tumor-associated fibroblasts were involved in tumor proliferation and progression. Read More

Pharmaceutics 2022 May 28;14(6). Epub 2022 May 28.

College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.

The epidermal growth factor receptor (EGFR) is highly expressed in many non-small cell lung cancers (NSCLC), necessitating the use of EGFR-tyrosine kinase inhibitors (TKIs) as first-line treatments. Osimertinib (OSM), a third-generation TKI, is routinely used in clinics, but T790M mutations in exon 20 of the EGFR receptor lead to resistance against OSM, necessitating the development of more effective therapeutics. Telmisartan (TLM), OSM, and cell cycle and apoptosis regulatory protein 1 (CARP-1) functional mimetic treatments (CFM4. Read More

Pharmaceuticals (Basel) 2022 Jun 2;15(6). Epub 2022 Jun 2.

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea.

Non-small cell lung cancer (NSCLC) is the most common lung cancer subtype. Although chemotherapy and targeted therapy are used for the treatment of patients with NSCLC, the survival rate remains very low. Recent findings suggested that aurora kinase A (AKA), a cell cycle regulator, is a potential target for NSCLC therapy. Read More

Molecules 2022 Jun 15;27(12). Epub 2022 Jun 15.

College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.

Epidermal growth factor receptor (EGFR) is an intensively focused target for anti-tumor compounds used in non-small cell lung cancer (NSCLC) therapy. Compared to the classical activating mutations, there are still many uncommon EGFR mutations associated with poorer responses to EGFR inhibitors. A detailed understanding of the molecular basis for multiple EGFR mutants exhibiting diverse responses to inhibitors is of critical importance for related drug development. Read More

Molecules 2022 Jun 14;27(12). Epub 2022 Jun 14.

Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. Read More

Micromachines (Basel) 2022 Jun 6;13(6). Epub 2022 Jun 6.

Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku 173-8605, Tokyo, Japan.

Liquid biopsy has been adapted as a diagnostic test for mutations in patients with advanced or metastatic non-small cell lung cancer (NSCLC). Loop-mediated isothermal amplification (LAMP) has been widely used for the rapid detection of pathogens through DNA amplification. This study investigated the efficacy of an -LAMP assay using plasma samples of patients with resected NSCLC tumors. Read More

Medicina (Kaunas) 2022 May 26;58(6). Epub 2022 May 26.

Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto 602-8026, Japan.

Pulmonary pleomorphic carcinoma (PPC) is well-known for its aggressive nature that is usually resistant to platinum-based chemotherapy. On the other hand, the efficacy of an immune checkpoint inhibitor-based regimen in PPC has been elucidated. PPCs harboring epidermal growth factor receptor (EGFR) mutations are extremely rare, and the efficacy of EGFR-tyrosine kinase inhibitors in PPC is limited compared to their efficacy in EGFR-mutated adenocarcinoma. Read More

J Pers Med 2022 May 30;12(6). Epub 2022 May 30.

Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

Lung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several cancer types. Read More

J Clin Med 2022 Jun 12;11(12). Epub 2022 Jun 12.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Patients with advanced non-small cell lung cancer (NSCLC) who harbor susceptible epidermal growth factor receptor (EGFR) mutations and are treated with EGFR tyrosine kinase inhibitors (TKIs) show longer progression-free survival (PFS) than those treated with chemotherapy. However, developed EGFR-TKI resistance limits PFS improvements. Currently, combination treatment with EGFR-TKIs and anti-angiogenic agents is considered a beneficial regimen for advanced-stage NSCLC harboring susceptible EGFR mutations. Read More

Int J Mol Sci 2022 Jun 17;23(12). Epub 2022 Jun 17.

Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Department of Medical Oncology, 33081 Aviano, Italy.

Standard treatment for advanced non-small cell lung cancer (NSCLC) historically consisted of systemic cytotoxic chemotherapy until the early 2000s, when precision medicine led to a revolutionary change in the therapeutic scenario. The identification of oncogenic driver mutations in EGFR, ALK and ROS1 rearrangements identified a subset of patients who largely benefit from targeted agents. However, since the proportion of patients with druggable alterations represents a minority, the discovery of new potential driver mutations is still an urgent clinical need. Read More

Int J Mol Sci 2022 Jun 10;23(12). Epub 2022 Jun 10.

Gynecologic Oncology Unit, ARNAS G. Brotzu, Department of Surgical Sciences, University of Cagliari, 09100 Cagliari, Italy.

Lung cancer is a leading cause of cancer-related deaths worldwide. About 10-30% of patients with non-small cell lung cancer (NSCLC) harbor mutations of the EGFR gene. The Tumor Microenvironment (TME) of patients with NSCLC harboring EGFR mutations displays peculiar characteristics and may modulate the antitumor immune response. Read More

Cancers (Basel) 2022 Jun 18;14(12). Epub 2022 Jun 18.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea.

The prevalence of multiple lung cancers has been increasing recently. Molecular analysis of epidermal growth factor receptor () mutations in individual tumors of multiple lung cancers is essential for devising an optimal therapeutic strategy. The mutation status in multiple lung cancers was evaluated to determine its therapeutic implications. Read More

Cancers (Basel) 2022 Jun 16;14(12). Epub 2022 Jun 16.

Pathology Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.

The approval of osimertinib for adjuvant treatment of stage I-II-III -mutated NSCLC (early stage) represents a paradigm shift, raising the question of whether other genotype-matched therapeutics approved for advanced-stage NSCLC can also provide clinical benefit in the adjuvant setting. However, there is a paucity of real-world data on the prevalence of actionable genomic alterations (GAs) in early-stage NSCLC. We used next-generation sequencing, complemented by immunohistochemistry and fluorescence in situ hybridization, to screen our single-institution cohort of 1961 NSCLC consecutive cases for actionable molecular targets. Read More