Search Our Scientific Publications & Authors

Gene 2019 Apr 17. Epub 2019 Apr 17.

Laboratory of Genetics and Molecular Pathology, Faculty of Medicine and Pharmacy of Casablanca, University Hassan II, Casablanca 20250, Morocco.

The study of EGFR gene mutational profile in NSCLC patients has a special clinical significance in the selection of patients for tyrosine-kinase inhibitors therapy. From 2017, the targeted therapy started to be accessible in public sector in Morocco, thus, the implementation of techniques for the molecular characterization of EGFR mutations in the laboratories became a necessity. The aim of this study was to present targeted methods "ADx-ARMS technology and the Idylla™ system" for the identification of EGFR mutational profile, methods that can be implemented in our clinical laboratories for routine analysis instead of outsourcing analysis to other countries. Read More

Sci Rep 2019 Apr 19;9(1):6301. Epub 2019 Apr 19.

Department of Medical Oncology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.

Dysregulated intratumoral immune reactions are shaped by complex networks of cytokines, which coordinate with tumor cells to determine tumor progression and aggressiveness. In lung adenocarcinoma (LUAD), the role of intratumoral cytokine gene expression for stratifying prognosis has not been systematically investigated. Using high-dimensional datasets of cancer specimens from clinical patients in The Cancer Genome Atlas (TCGA), we explored the transcript abundance and prognostic impact of 27 clinically evaluable cytokines in 500 LUAD tumor samples according to clinicopathological features and two common driver mutations (EGFR and KRAS). Read More

J Thorac Oncol 2019 Apr 16. Epub 2019 Apr 16.

Guangdong Lung Cancer Institute; Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences; Guangzhou; China.

In 2018 research in the field of advanced non-small cell lung cancers (NSCLC) led to an expanded reach and impact of immune-checkpoint inhibitors (ICIs) as part of frontline treatment strategy, regardless of histology subtype, while ICI use was extended to include stage III disease, shifting the prognosis of all these patients. This new standard first-line approach opens a gap in standard second-line treatment, and older combinations may again become standard care after progression on ICIs. The characterization of predictive biomarkers, patient selection, the definition of strategies with ICI combinations upon progression on ICIs, as well as prospective evaluation of the efficacy of ICIs in subpopulations (such as patients with poor performance status or brain metastases) represent upcoming challenges in advanced thoracic malignancies. Read More

Acta Oncol 2019 Apr 19:1-8. Epub 2019 Apr 19.

b 2nd Department of Pathology, MTA-SE NAP Brain Metastasis Research Group Hungarian Academy of Sciences , Semmelweis University , Budapest , Hungary.

Background: Predictive biomarkers for immunotherapy in lung cancer are intensively investigated; however, correlations between PD-L1/PD-1 expressions and clinical features or histopathological tumor characteristics determined on hematoxylin and eosin stained sections have not extensively been studied.

Material And Methods: We determined PD-L1 expression of tumor cells (TC) and immune cells (IC), and PD-1 expression of IC by immunohistochemistry in 268 lung adenocarcinoma (LADC) patients, and correlated the data with smoking, COPD, tumor grade, necrosis, lepidic growth pattern, vascular invasion, density of stromal IC, and EGFR/KRAS status of the tumors.

Results: There was a positive correlation between PD-L1 expression of TC and IC, as well as PD-L1 and PD-1 expression of IC. Read More

Nat Commun 2019 Apr 18;10(1):1812. Epub 2019 Apr 18.

Laboratory of Oncology, Pangaea Oncology, Quiron Dexeus University Hospital, 08028, Barcelona, Spain.

Non-small cell lung cancer (NSCLC) tumors harboring mutations in EGFR ultimately relapse to therapy with EGFR tyrosine kinase inhibitors (EGFR TKIs). Here, we show that resistant cells without the p.T790M or other acquired mutations are sensitive to the Aurora B (AURKB) inhibitors barasertib and S49076. Read More

Cancer Med 2019 Apr 17. Epub 2019 Apr 17.

National Centre for Cell Science, SP Pune University Campus, Pune, India.

Lung cancer is the leading cause of deaths related to cancer and accounts for more than a million deaths per year. Various new strategies have been developed and adapted for treatment; still the survival for 5 years is just 16% in patients with non-small cell lung cancer (NSCLC). Most of these strategies to combat NSCLC whether it is a drug molecule or immunotherapy/vaccine candidate require a big cost and time. Read More

J Thorac Dis 2019 Mar;11(Suppl 3):S448-S452

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

J Thorac Dis 2019 Mar;11(Suppl 3):S249-S252

Thoracic Oncology Unit, Santa Maria della Misericordia Hospital, University of Perugia, Piazzale Menghini, Perugia, Italy.

Future Med Chem 2019 Apr 17. Epub 2019 Apr 17.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo NSW 2007, Australia.

Bioanalysis 2019 Apr 17. Epub 2019 Apr 17.

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100032, PR China.

BPI15086 is a potent, irreversible mutant-selective inhibitor of both EGFR (EGFR tyrosine kinase inhibitor) and the T790M resistance mutations tyrosine kinase. A simultaneous quantification method of BPI15086 and its main metabolite in human plasma using LC-MS/MS is documented and fully validated in this study. Plasma samples were extracted and chromatographed on an Acquity ultra-high performance liquid chromatography BEH C18 column with a gradient elution. Read More

Cancer Med 2019 Apr 16. Epub 2019 Apr 16.

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China.

Background: Leptomeningeal metastasis (LM) is a detrimental complication of advanced non-small-cell lung cancer (NSCLC), and the optimal therapeutic approach for LM patients is in shortage. This retrospective study aimed to investigate the clinical features and prognostic factors of NSCLC patients with LM.

Methods: We retrospectively reviewed the medical records of NSCLC patients with LM at the Shandong Cancer Hospital and Institute between July 2014 and March 2018. Read More

Arch Toxicol 2019 Apr 16. Epub 2019 Apr 16.

Department of Occupational and Environmental Health Sciences, School of Public Health, West Virginia University, PO Box 9190, 3302 Health Sciences Center, HSC South, 64 Medical Center Drive, Morgantown, WV, 26506, USA.

The T790M mutation is recognized as a typical mechanism of acquired resistance to first generation of epithermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib in non-small cell lung cancer (NSCLC) patients who are commonly treated by third generation of EGFR-TKI AZD9291 (osimertinib). However, the therapeutic strategy for overcoming acquired resistance to EGFR-TKIs in NSCLC patients without T790M remains to be definitively determined. In the present study, gefitinib-resistant H1650 (H1650GR) or AZD9291-resistant H1975 (H1975AR) was generated by exposing NSCLC cell line H1650 or H1975 to progressively increased concentrations of gefitinib or AZD9291 over 11 months. Read More

J Cytol 2019 Apr-Jun;36(2):124-127

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Lung cancer (LC) is the leading cause of cancer-related mortality. Unfortunately, most patients of LC present at the advanced stage of the disease with a poor prognosis and 1-year survival of less than 20%. At the advanced stage of the disease, surgical resection cannot be possible, hence small biopsy or cytology specimens remain a choice for their correct diagnosis. Read More

Nat Commun 2019 Apr 16;10(1):1772. Epub 2019 Apr 16.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, 510080, Guangzhou, China.

Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72. Read More

Cancer Biol Ther 2019 Apr 16:1-8. Epub 2019 Apr 16.

a Department of Respiratory Medicine , Center for Molecular Medicine, Xiangya Hospital , Central South University , Changsha , China.

Literatures regarding the prevalence and clinical significance of compound EGFR mutations are limited. Until now, none of retrospective or prospective research has focused on in cis compound EGFR mutations except case reports. In this study, we screened a cohort of 3,000 treatment-naïve Chinese advanced NSCLC patients using capture-based ultra-deep targeted sequencing to evaluate the prevalence of EGFR in cis compound mutations and the efficacy of EGFR-TKI in this population. Read More

J Neurooncol 2019 Apr 16. Epub 2019 Apr 16.

Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham and Women's Hospital, 60 Fenwood Rd., 4th Floor, Boston, MA, 02115, USA.

Purpose: While surgery and radiation remain the mainstays of therapy for all patients with brain metastases (BM), the management is moving to a more individualized approach based on the underlying tumor. We sought to identify prognostic factors of both intracranial progression (IC-PFS) and overall survival (OS) in a surgical cohort.

Methods: We retrospectively reviewed the records of 1015 patients treated surgically for BM at Brigham and Women's Hospital (2007-2017). Read More

Clin Cancer Res 2019 Apr 15. Epub 2019 Apr 15.

Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center.

Purpose: Complete and timely tissue genotyping is challenging, leading to significant numbers of patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) being undergenotyped for all eight genomic biomarkers recommended by professional guidelines. We aimed to demonstrate non-inferiority of comprehensive cell-free DNA (cfDNA) relative to physician discretion standard-of-care (SOC) tissue genotyping to identify guideline-recommended biomarkers in patients with mNSCLC.

Experimental Design: Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretion SOC tissue genotyping submitted a pre-treatment blood sample for comprehensive cfDNA analysis (Guardant360). Read More

BMC Cancer 2019 Apr 15;19(1):353. Epub 2019 Apr 15.

Ohio State University Medical Center, Columbus, OH, USA.

Background: Locally advanced or metastatic non-small cell lung cancer (NSCLC) that has progressed after first-line treatment has a poor prognosis. Recent randomized clinical trials (RCTs) have demonstrated survival benefits of alternative treatments to docetaxel. However, information is lacking on which patients benefit the most and what drug or regimen is optimal. Read More

Front Oncol 2019 29;9:195. Epub 2019 Mar 29.

Division of Medical Oncology, Department of Internal Medicine, University of Colorado Cancer Center, Aurora, CO, United States.

Inhibitory antibodies targeting programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have resulted in improved outcomes for many patients with metastatic non-small cell lung cancer in (NSCLC) in the second-line setting due to their ability to lead to prolonged anti-tumor immune responses. Combining these immunotherapies with platinum-based chemotherapy as first-line treatment has resulted in improved response rates and increased survival when compared to platinum-based chemotherapy alone. Certain patient populations may even benefit from immune checkpoint inhibitors as monotherapy in the first-line setting. Read More

Balkan J Med Genet 2018 Dec 31;21(2):21-26. Epub 2018 Dec 31.

Medical Biology Department, Pamukkale University, Denizli Turkey.

In this study, profiles of epidermal growth factor receptor (EGFR) and Kirsten ras sarcoma (KRAS) mutations and response to erlotinib therapy have been investigated in patients with non-small cell lung cancer (NSCLC). DNA from 300 patients with NSCLC was extracted from paraf-fin-embedded tissues. After the extracted DNA was sequenced by pyrosequencing method, a total of 97 (32. Read More

J Med Genet 2019 Apr 13. Epub 2019 Apr 13.

Department of Medical Oncology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

Background: Early detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumour (ct) DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery.

Methods: The multicentre clinical study enrolled 192 patients with operable occupying lung diseases. Read More

Diagnostics (Basel) 2019 Apr 11;9(2). Epub 2019 Apr 11.

Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081 Aviano, Italy.

Most non-small-cell lung cancer (NSCLC) patients are likely to develop brain metastases during the course of their illness. Currently, no consensus on NSCLC patients' treatment with brain metastasis has been established. Although whole brain radiotherapy prolongs the median survival time of approximately 4 months, a cisplatin-pemetrexed combination may also represent a potential option in the treatment of asymptomatic NSCLC patients with brain metastases. Read More

J Thorac Oncol 2019 Apr 9. Epub 2019 Apr 9.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong. Electronic address:

Introduction: Patients with pulmonary large cell carcinoma (LCC) have poor prognosis and limited treatment option. The identification of clinically actionable molecular alterations helps to guide personalized cancer treatment decisions.

Patients And Methods: A consecutive cohort of 789 resected non-small cell lung carcinomas (NSCLCs) were reviewed. Read More

PLoS One 2019 12;14(4):e0215292. Epub 2019 Apr 12.

Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan.

Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. Read More

Open Access Maced J Med Sci 2019 Mar 27;7(6):973-977. Epub 2019 Mar 27.

Section of Dermatology, University of Naples Federico II, Naples, Italy via Sergio Pansini 5, 80131 Naples, Italy.

Background: Tyrosine kinase inhibitors (TKIs) have been introduced for the treatment of lung cancer, improving progression-free survival, objective response rate, and quality of life. However, TKIs can lead to cutaneous toxicities, including papulopustular rash, xerosis, paronychia with/without pyogenic granulomas, scalp disorders, facial hair and/or eyelash growth.

Aim: In this study, we describe retrospectively all cases of mucocutaneous side effects in patients with lung cancer under TKIs referring to our outpatient for the skin care of oncological patients. Read More

Oncologist 2019 Apr 11. Epub 2019 Apr 11.

Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada.

Background: Seribantumab (MM-121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 () to block heregulin ()-mediated signaling and induce receptor downregulation. This open-label, randomized phase 1/2 study evaluated safety and efficacy of seribantumab plus erlotinib in advanced non-small cell lung cancer (NSCLC). Here, we report the activity of seribantumab plus erlotinib, versus erlotinib alone, in patients with wild-type tumors and describe the potential predictive power of HRG. Read More

Lancet Oncol 2019 Apr 8. Epub 2019 Apr 8.

Iwate Medical University School of Medicine, Morioka, Japan. Electronic address:

Background: Resistance to first-generation or second-generation EGFR tyrosine kinase inhibitor (TKI) monotherapy develops in almost half of patients with EGFR-positive non-small-cell lung cancer (NSCLC) after 1 year of treatment. The JO25567 phase 2 trial comparing erlotinib plus bevacizumab combination therapy with erlotinib monotherapy established the activity and manageable toxicity of erlotinib plus bevacizumab in patients with NSCLC. We did a phase 3 trial to validate the results of the JO25567 study and report here the results from the preplanned interim analysis. Read More

J Exp Clin Cancer Res 2019 Apr 11;38(1):157. Epub 2019 Apr 11.

Affiliated Cancer Hospital and institute of Guangzhou Medical University; Key Laboratory of Protein Modification and Degradation; State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, Guangdong, China.

Background: Prostate cancer (PCa) remains a challenge worldwide. Due to the development of castration-resistance, traditional first-line androgen deprivation therapy (ADT) became powerlessness. Epidermal growth factor receptor (EGFR) is a well characterized therapeutic target to treat colorectal carcinoma and non-small cell lung cancer. Read More

Pharmacol Res 2019 Apr 8;144:79-89. Epub 2019 Apr 8.

State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute For Applied Research in Medicine and Health, Macau University of Science and Technology, Macau (SAR), China; Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, Guangdong, China. Electronic address:

Lung cancer is the most commonly diagnosed cancer worldwide and it is also the most leading cause of cancer-related deaths. Although multiple generations of targeted therapeutic drugs such as gefitinib and afatinib specifically targeting the epidermal growth factor receptor (EGFR) pathway are currently available for lung cancer treatment, none of them can escape their eventual drug-resistance. As a key component of Cordyceps Sinensis and widely used in traditional Chinese medicines (TCM), cordycepin (CD) has attracted increasing attention to both scientists and clinicians. Read More

PLoS One 2019 11;14(4):e0215135. Epub 2019 Apr 11.

Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium.

Introduction: Little data is available on patients with advanced non-squamous NSCLC treated with erlotinib specifically after failure of first-line pemetrexed-containing chemotherapy. We assessed the effectiveness, safety and tolerability of erlotinib in a real-world setting.

Methods: Prospective single-arm, open-label, multicenter, non-interventional study of erlotinib (150mg daily) in inoperable stage III/IV NSCLC after progression on first-line pemetrexed-containing chemotherapy without EGFR-mutation selection. Read More

Cancer Sci 2019 Apr 10. Epub 2019 Apr 10.

Department of Genome Biology, Kindai University, Faculty of Medicine, Osaka, Japan.

Gene fusions play an important role in the carcinogenesis of lung adenocarcinoma. The recent association of four oncogenic driver genes, ALK, ROS1, RET, and NTRK1, as lung tumor predictive biomarkers has increased the need for precision medicine. We used formalin-fixed, paraffin-embedded tissue samples of non-small cell lung cancer from 150 EGFR mutation-negative cases and 10 fusion status-known cases and compared the performance of the Oncomine Dx Fusion Transcript Test (ODxFT) with FISH Break Apart for the detection of ALK, RET, and ROS1 fusion genes. Read More

J Pathol 2019 Apr 11. Epub 2019 Apr 11.

Department of Medical Oncology, Cancer Research Center Groningen, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have improved the survival of patients with non-small cell lung cancer (NSCLC). Still, many patients do not respond to these inhibitors. PD-L1 (CD274) expression, one of the factors that influences efficacy of immune checkpoint inhibitors, is dynamic. Read More

Front Pharmacol 2019 22;10:260. Epub 2019 Mar 22.

Department of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Cancer cells are characterized by abnormally increased glucose uptake and active bio-energy and biosynthesis to support the proliferation, metastasis, and drug resistant survival. We examined the therapeutic value of the combination of apigenin (a natural small-molecule inhibitor of Glut1 belonging to the flavonoid family) and gefitinib on epidermal growth factor receptor (EGFR)-resistant mutant non-small cell lung cancer, to notably damage glucose utilization and thus suppress cell growth and malignant behavior. Here, we demonstrate that apigenin combined with gefitinib inhibits multiple oncogenic drivers such as c-Myc, HIF-1α, and EGFR, reduces Gluts and MCT1 protein expression, and inactivates the 5' adenosine monophosphate-activated protein kinase (AMPK) signaling, which regulates glucose uptake and maintains energy metabolism, leading to impaired energy utilization in EGFR L858R-T790M-mutated H1975 lung cancer cells. Read More

JAMA 2019 04;321(14):1391-1399

Foundation Medicine Inc, Cambridge, Massachusetts.

Importance: Data sets linking comprehensive genomic profiling (CGP) to clinical outcomes may accelerate precision medicine.

Objective: To assess whether a database that combines EHR-derived clinical data with CGP can identify and extend associations in non-small cell lung cancer (NSCLC).

Design, Setting, And Participants: Clinical data from EHRs were linked with CGP results for 28 998 patients from 275 US oncology practices. Read More

J Thorac Dis 2019 Feb;11(2):595-601

Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.

Malignant pleural effusion (MPE) is an indicator of advanced disease (stage M1a) in patients with non-small cell lung cancer (NSCLC). Typically, these patients are candidates for palliative treatment. There is a lack of evidence about the radical surgical treatment in carcinomatous pleuritis with massive effusion. Read More

Yonago Acta Med 2019 Mar 28;62(1):85-93. Epub 2019 Mar 28.

Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.

Background: The epidermal growth factor receptor (EGFR) is a therapeutic target for patients with non-small cell lung cancer (NSCLC). Cetuximab is an anti-EGFR monoclonal antibody that inhibits EGFR signaling and proliferation of colorectal cancer and head and neck cancers. Since only few NSCLC patients benefit from cetuximab therapy, we evaluated a novel combination treatment using cetuximab and small interfering RNA (siRNA) to strongly suppress EGFR signaling and searched for a biomarker in NSCLC cell lines harboring wild-type . Read More

Lung Cancer (Auckl) 2019 20;10:27-36. Epub 2019 Mar 20.

Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy,

Non-small-cell lung cancer (NSCLC) patients with mutated or rearranged oncogene drivers can be treated with upfront selective inhibitors achieving higher response rates and longer survival than chemotherapy. The RET gene can undergo chromosomal rearrangements in 1%-2% of all NSCLC patients, involving various upstream fusion partners such as KIF5B, CCDC6, NCOA4, and TRIM33. Many multikinase inhibitors are active against rearranged RET. Read More

Cancer Manag Res 2019 21;11:2269-2280. Epub 2019 Mar 21.

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China,

Purpose: The prognostic value of tumor location in pulmonary adenocarcinoma (ADC) is controversial. We compared the prognosis and relevant data between central-type ADC (CT-ADC) and peripheral-type ADC (PT-ADC) in order to identify the reasons for the different outcomes between them and to improve the treatment strategy and prognosis of these two types.

Patients And Methods: Data of 256 patients with pathologically diagnosed ADC were retrospectively reviewed. Read More

Pathol Res Pract 2019 Apr 1. Epub 2019 Apr 1.

Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. Electronic address:

Objective: Lung adenocarcinoma in young patients is a rare entity, and the targetable genomic alterations (GAs) are poorly studied. In other cancers, it has been demonstrated that young age defines unique disease biology. Here, the association of young age with GAs and prognosis is studied in a large cohort of Chinese patients. Read More

BMC Cancer 2019 Apr 8;19(1):336. Epub 2019 Apr 8.

Department of Respiratory Medicine, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-0824, Japan.

Background: Abscopal effect is the out-of-field response to localized irradiation therapy that results in systemic antitumorigenic effects such as the regression of a tumor distant from the target site.

Case Presentation: A 76-year-old woman was diagnosed with pulmonary adenocarcinoma (cT1bN0M0 stage IA), and right upper lobectomy was performed in November 2015. The pathological stage was pT1bN2M0 stage IIIA. Read More

Cells 2019 Apr 5;8(4). Epub 2019 Apr 5.

Department of Chemistry, University College London, London WC1H 0AJ, UK.

The epidermal growth factor receptor (EGFR) is historically the prototypical receptor tyrosine kinase, being the first cloned and the first where the importance of ligand-induced dimer activation was ascertained. However, many years of structure determination has shown that EGFR is not completely understood. One challenge is that the many structure fragments stored at the PDB only provide a partial view because full-length proteins are flexible entities and dynamics play a key role in their functionality. Read More

Int J Cancer 2019 Apr 7. Epub 2019 Apr 7.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

Afatinib is a pan-HER inhibitor approved for specific types of lung cancer. We explored antitumor activity, predictive biomarkers and the potential mechanisms underlying antitumor effect and acquired resistance of afatinib in gastric cancer (GC) in vitro and in vivo. Five human GC cell lines and eight patient-derived xenograft (PDX) models with clear molecular profiling were used to evaluate the antitumor activity and mechanisms of afatinib. Read More

Lancet 2019 Apr 4. Epub 2019 Apr 4.

Department of Medical Oncology, Sylvester Comprehensive Cancer Center at the University of Miami, Miami, FL, USA.

Background: First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.

Methods: This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Read More

Zhonghua Bing Li Xue Za Zhi 2019 Apr;48(4):270-275

Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

The diagnostic criteria of lung biopsy specimens by 2015 WHO lung tumor classification were used to evaluate lung biopsy specimens along with detection of genetic alterations of major tumor driving genes including epidermal growth factor receptor (EGFR). The clinical data, histological slides, immunohistochemical stains and special stains of 806 lung biopsy specimens at Beijing Hospital from July 2015 to July 2018 were retrospectively analyzed. Diagnosis of lung cancer was reclassified according to the 2015 WHO lung tumor classification and related gene mutation data were analyzed. Read More

Cancer Treat Rev 2019 Mar 28;75:39-51. Epub 2019 Mar 28.

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

Immunotherapy has dramatically changed the therapeutic scenario in treatment naïve advanced non-small cell lung cancer (NSCLC). While single agent pembrolizumab has become the standard therapy in patients with PD-L1 expression on tumor cells ≥ 50%, the combination of pembrolizumab or atezolizumab and platinum-based chemotherapy has emerged as an effective first line treatment regardless of PD-L1 expression both in squamous and non-squamous NSCLC without oncogenic drivers. Furthermore, double immune checkpoint inhibition has shown promising results in treatment naïve patients with high tumor mutational burden (TMB). Read More

Gene 2019 Apr 4;703:58-64. Epub 2019 Apr 4.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

This study was conducted to explore whether polymorphisms of glucose transporter 3 (GLUT3) gene affect the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Four single nucleotide polymorphisms (SNPs) in GLUT3 were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. Read More

J Exp Clin Cancer Res 2019 Apr 5;38(1):148. Epub 2019 Apr 5.

Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China.

Background: Recent Clinical trials of administration of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with standard first-line chemotherapy have failed to improve survival in patients with advanced NSCLC, However, the sequential treatment with EGFR-TKIs and chemotherapy is expected to improve survival of NSCLC. The aim of this study is to test the antiproliferative effect of pemetrexed combined with icotinib in different sequences on non-small cell lung cancer (NSCLC) cell lines to determine the optimal combination schedule, and subsequently elaborated the potential mechanisms.

Methods: Six human lung cancer cell lines with wild-type or mutant EGFR gene were exposed to pemetrexed and icotinib combined in different sequences. Read More

Int J Clin Oncol 2019 Apr 5. Epub 2019 Apr 5.

Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan.

Background: This prospective, post-marketing observational study in Japanese patients aimed to evaluate the safety and effectiveness of daily afatinib use in general practice.

Methods: This non-interventional study (NCT02131259) enrolled treatment-naïve and pre-treated patients with inoperable/recurrent EGFR mutation-positive NSCLC, eligible for afatinib treatment as per the afatinib label in Japan. Patients received afatinib at the approved dose (20, 30, 40, or 50 mg/day; physician decision), and were observed following treatment initiation for 52 weeks or until premature discontinuation. Read More

Sci Rep 2019 Apr 5;9(1):5692. Epub 2019 Apr 5.

Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang, P.R. China.

PCC-0208027 is a novel tyrosine kinase inhibitor that has a strong inhibitory effect on epidermal growth factor receptor (EGFR)- or HER2-driven cancers. The aim is to assess the anti-tumor activity of PCC0208027 and related mechanisms in non-small cell lung cancer (NSCLC). We examined the activity of PCC0208027 on various mutated EGFRs, HER2, and HER4. Read More

Oncologist 2019 Apr 5. Epub 2019 Apr 5.

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy

Background: HER2 amplification is detected in 3% of patients with colorectal cancer (CRC), making tumors in the metastatic setting vulnerable to double pharmacological HER2 blockade. Preclinical findings show that it also might impair response to anti-epidermal growth factor receptor (EGFR) treatment.

Subjects And Methods: Patients with exon 2 wild-type metastatic CRC underwent molecular screening of HER2 positivity by HERACLES criteria (immunohistochemistry 3+ or 2+ in ≥50% of cells, confirmed by fluorescence in situ hybridization). Read More