scholarly journals Exosomes: a new perspective in EGFR-mutated lung cancer

2021 ◽  
Author(s):  
Amina Jouida ◽  
Cormac McCarthy ◽  
Aurelie Fabre ◽  
Michael P. Keane
Keyword(s):  
Lung Cancer ◽  
Cell Communication ◽  
Egfr Mutations ◽  
Functional Effect ◽  
Prognosis And Prediction ◽  
Novel Biomarkers ◽  
New Perspective ◽  
Source Of Information ◽  
Egfr Mutated

AbstractExosomes are major contributors in cell to cell communication due to their ability to transfer biological material such as protein, RNA, DNA, and miRNA. Additionally, they play a role in tumor initiation, promotion, and progression, and recently, they have emerged as a potential source of information on tumor detection and may be useful as diagnostic, prognostic, and predictive tools. This review focuses on exosomes from lung cancer with a focus on EGFR mutations. Here, we outline the role of exosomes and their functional effect in carcinogenesis, tumor progression, and metastasis. Finally, we discuss the possibility of exosomes as novel biomarkers in early detection, diagnosis, assessment of prognosis, and prediction of therapeutic response in EGFR-mutated lung cancer.

scholarly journals From Exosome Glycobiology to Exosome Glycotechnology, the Role of Natural Occurring Polysaccharides

2021 ◽  
Vol 2 (2) ◽  
pp. 311-338
Author(s):  
Giulia Della Rosa ◽  
Clarissa Ruggeri ◽  
Alessandra Aloisi
Keyword(s):  
State Of The Art ◽  
Cell Communication ◽  
Pathological Conditions ◽  
New Findings ◽  
Cell Type Specific ◽  
New Perspective ◽  
And Function ◽  
And Personalized Medicine ◽  
Innate Ability

Exosomes (EXOs) are nano-sized informative shuttles acting as endogenous mediators of cell-to-cell communication. Their innate ability to target specific cells and deliver functional cargo is recently claimed as a promising theranostic strategy. The glycan profile, actively involved in the EXO biogenesis, release, sorting and function, is highly cell type-specific and frequently altered in pathological conditions. Therefore, the modulation of EXO glyco-composition has recently been considered an attractive tool in the design of novel therapeutics. In addition to the available approaches involving conventional glyco-engineering, soft technology is becoming more and more attractive for better exploiting EXO glycan tasks and optimizing EXO delivery platforms. This review, first, explores the main functions of EXO glycans and associates the potential implications of the reported new findings across the nanomedicine applications. The state-of-the-art of the last decade concerning the role of natural polysaccharides—as targeting molecules and in 3D soft structure manufacture matrices—is then analysed and highlighted, as an advancing EXO biofunction toolkit. The promising results, integrating the biopolymers area to the EXO-based bio-nanofabrication and bio-nanotechnology field, lay the foundation for further investigation and offer a new perspective in drug delivery and personalized medicine progress.

scholarly journals Prognostic role of circulating tumor cells in patients with EGFR -mutated or ALK -rearranged non-small cell lung cancer

2018 ◽  
Vol 9 (5) ◽  
pp. 640-645 ◽  
Author(s):  
Bing Tong ◽  
Yan Xu ◽  
Jing Zhao ◽  
Minjiang Chen ◽  
Wei Zhong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Prognostic Role ◽  
Egfr Mutated

scholarly journals Field Cancerization in NSCLC: A New Perspective on MicroRNAs in Macrophage Polarization

2021 ◽  
Vol 22 (2) ◽  
pp. 746
Author(s):  
Radu Pirlog ◽  
Andrei Cismaru ◽  
Andreea Nutu ◽  
Ioana Berindan-Neagoe
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Respiratory Tract ◽  
Macrophage Polarization ◽  
Cell Communication ◽  
Premalignant Lesions ◽  
Field Cancerization ◽  
Dynamic Interactions ◽  
Lung Cancers ◽  
New Perspective

Lung cancer is currently the first cause of cancer-related death. The major lung cancer subtype is non-small cell lung cancers (NSCLC), which accounts for approximatively 85% of cases. The major carcinogenic associated with lung cancer is tobacco smoke, which produces long-lasting and progressive damage to the respiratory tract. The progressive and diffuse alterations that occur in the respiratory tract of patients with cancer and premalignant lesions have been described as field cancerization. At the level of tumor cells, adjacent tumor microenvironment (TME) and cancerized field are taking place dynamic interactions through direct cell-to-cell communication or through extracellular vesicles. These molecular messages exchanged between tumor and nontumor cells are represented by proteins, noncoding RNAs (ncRNAs) and microRNAs (miRNAs). In this paper, we analyze the miRNA roles in the macrophage polarization at the level of TME and cancerized field in NSCLC. Identifying molecular players that can influence the phenotypic states at the level of malignant cells, tumor microenvironment and cancerized field can provide us new insights into tumor regulatory mechanisms that can be further modulated to restore the immunogenic capacity of the TME. This approach could revert alterations in the cancerized field and could enhance currently available therapy approaches.

Response with pemrbolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R

2021 ◽  
pp. 107815522110578
Author(s):  
Matthew J. Hadfield ◽  
Alla Turshudzhyan ◽  
Khalid Shalaby ◽  
Aswanth Reddy
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Durable Response ◽  
Egfr Mutated

Introduction Lung cancer is the leading cause of cancer-related deaths with non-small cell lung cancer (NSCLC) being the most common of them. About a third of NSCLC cases have an epidermal growth factor (EGFR) mutation, which is usually susceptible to tyrosine kinase inhibitors (TKIs). In rare cases where patients progress through TKI therapy, the use of immune checkpoint inhibitors (ICIs) remains controversial. Case report We describe a case of a patient with significant history of smoking and EGFR mutated programmed death ligand-1 (PD-L1) positive NSCLC who was initially treated with TKI therapy. Management/Outcome While patient progressed on TKI therapy, he was able to achieve a durable response with a single PD-L1 agent, pembrolizumab. Contrary to the available evidence, the presented EGFR mutant NSCLC responded to PD-L1 pathway inhibition. Discussion From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.

Family history of lung cancer in never smokers with non-small cell lung cancer (NSCLC) and its association with tumors harboring epidermal growth factor receptor (EGFR) mutations.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7579-7579
Author(s):  
Elizabeth Mary Gaughan ◽  
Sarah K Cryer ◽  
Beow Yong Yeap ◽  
David Michael Jackman ◽  
Daniel Botelho Costa
Keyword(s):  
Lung Cancer ◽  
Family History ◽  
Medical Center ◽  
Egfr Mutations ◽  
Tumor Type ◽  
Kras Mutations ◽  
Inherited Susceptibility ◽  
History Of ◽  
Never Smokers ◽  
Egfr Mutated

7579 Background: Inherited susceptibility to lung cancer is an understudied subject, however it has been described among never smokers (<100 cigarettes/lifetime). Never smokers with NSCLC comprise an important subgroup of patients enriched for tumors harboring oncogene aberrations in the EGFR and ALK genes. We aimed to better characterize the incidence of family history of lung cancer in the setting of routine tumor genotyping among never smokers with NSCLC. Methods: Clinicopathologic data plus tumor genotype (EGFR, KRAS, ALK) from 230 consecutive never smokers seen at Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute was compiled. We retrospectively analyzed the incidence of a family history of any cancer and lung cancer in these patients. Results: In our cohort, the average age was 56 years, 67% of the patients were women, 75% were white, 41% had advanced NSCLC and 87% had adenocarcinoma histology. In these tumors, 98/230 (43%) had an EGFR mutation, 16/155 (10%) had KRAS mutations and 27/127 (17%) had an ALK translocation. Family history of any cancer was common (57%) and specific family history of lung cancer was present in 42/230 cases (18%). Out of thecases with a family history of any cancer, 22/53 (41.5%) EGFR-mutated, 1/6 (17%) KRAS-mutated and 3/20 (15%) ALK-translocated cohorts had a family history of lung cancer. The rate of family history of lung cancer to family history of cancer was significantly higher in the EGFR-mutated cohort when compared to the ALK translocated plus KRAS-mutated cohorts (p=0.023). Conclusions: Family history of lung cancer is common in never smokers with NSCLC, and there seems to be a particular link in families in which the proband has an EGFR-mutated tumor. Further study of families with EGFR-mutated NSCLC may yield insights into the pathogenesis of this tumor type.

scholarly journals Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients

2019 ◽  
Vol 21 (1) ◽  
pp. 66
Author(s):  
Elisa Boldrin ◽  
Giorgia Nardo ◽  
Elisabetta Zulato ◽  
Laura Bonanno ◽  
Valentina Polo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Loss Of Heterozygosity ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Genetic Characteristics ◽  
Nsclc Patients ◽  
Egfr Mutated

Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays.

Outcomes of KRAS mutated, EGFR mutated, ALK mutated and wildtype patients in non-small cell lung cancer brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21028-e21028
Author(s):  
Yasmeen Rauf ◽  
Vineeth Tatineni ◽  
Patrick joseph Oshea ◽  
Xuefei Jia ◽  
David M. Peereboom ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Retrospective Study ◽  
Brain Metastases ◽  
Targeted Therapies ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Alk Positive ◽  
Egfr Mutated

e21028 Background: Non-small cell lung cancer (NSCLC) is the most common primary tumor leading to brain metastases. Multiple genetic markers have been profiled in NSCLC patients for potential targeted therapies. EGFR is mutated in up 50% of NSCLCs, while ALK is mutated in around 4-7%. KRAS is the most commonly overexpressed marker, seen in up to 85% of all lung cancers. In this retrospective study, we evaluated the overall survival (OS) and progression-free survival (PFS) between NSCLCBM patients with KRAS mutations, ALK mutations, EGFR mutations, and wildtype. Methods: NSCLCBM patients diagnosed between 2010 and 2019 were analyzed. We collected information regarding molecular marker status, systemic therapies, and date of progression. We defined OS as the date of diagnosis of brain metastases to the date of last follow-up or death. OS and PFS were estimated by the Cox proportional model. Results: We found a total of 2989 NCSLCBM patients, 184 were KRAS mutated, 68 had an ALK gene rearrangement, 184 were EGFR mutated, and 1469 were wildtype. The respective median age was 64.3 years, 64.5 years, 58.2 years, and 64.2 years. Females made up 61.8% of KRAS-positive, 51.8% of ALK-positive, 63% of EGFR-positive, and 46.4% of wildtype patients. The median OS (mOS) in patients who were KRAS-positive, ALK-positive, EGFR-positive, and wildtype were 43.3 months, 119.2 months, 57.9 months, and 33.1 months, respectively. The median PFS (mPFS) for the same cohort was 38.0 months, 112.4 months, 55.3 months, and 30.5 months, respectively. ALK-positive patients showed statistically significant mOS (p-value (p) < 0.001) and mPFS (p = 0.002) when compared to EGFR-positive, KRAS-positive, and wildtype patients. Conclusions: Molecular mutations serve as both prognostic predictors and alternative targeted therapies for NSCLCBM treatment. Our retrospective study showed improved mOS and mPFS in NSCLCBM patients with ALK rearrangements when compared to patients with EGFR mutations, KRAS mutations, and the wildtype. While these results looked at patient outcomes with specific tumor markers, further investigation needs to be done regarding outcomes of specific therapies in each cohort, as well as, intracranial lesion response.

scholarly journals EGFR‐mutated stage IV non‐small cell lung cancer: What is the role of radiotherapy combined with TKI?

2021 ◽  
Author(s):  
Bailong Liu ◽  
Hui Liu ◽  
Yunfei Ma ◽  
Qiuhui Ding ◽  
Min Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutated

scholarly journals Tyrosine Kinase Receptor Landscape in Lung Cancer: Therapeutical Implications

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
A. Quintanal-Villalonga ◽  
Luis Paz-Ares ◽  
Irene Ferrer ◽  
S. Molina-Pinelo
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Receptors ◽  
Tyrosine Kinase Receptor ◽  
Poor Survival ◽  
Advanced Stages ◽  
Novel Biomarkers ◽  
New Biomarkers ◽  
Molecular Nature

Lung cancer is a heterogeneous disease responsible for the most cases of cancer-related deaths. The majority of patients are clinically diagnosed at advanced stages, with a poor survival rate. For this reason, the identification of oncodrivers and novel biomarkers is decisive for the future clinical management of this pathology. The rise of high throughput technologies popularly referred to as “omics” has accelerated the discovery of new biomarkers and drivers for this pathology. Within them, tyrosine kinase receptors (TKRs) have proven to be of importance as diagnostic, prognostic, and predictive tools and, due to their molecular nature, as therapeutic targets. Along this review, the role of TKRs in the different lung cancer histologies, research on improvement of anti-TKR therapy, and the current approaches to manage anti-TKR resistance will be discussed.

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