Biomarker for Non-small Cell Lung Cancer: From the Bench to the Bedside

A topical collection in Journal of Clinical Medicine (ISSN 2077-0383). This collection belongs to the section "Oncology".

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Editor


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Guest Editor
1. Post-Graduation Program in Medicine, Precision Oncology & Health Economics Group, Nine of July University, São Paulo, Brazil
2. Division of Medical Oncology, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil
3. Algarve Biomedical Centre, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal
Interests: immunotherapy; lung cancer; targeted therapy; predictive biomarkers; prognostic biomarker
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Lung cancer is a very aggressive disease. Currently, personalizing medicine has acquired a main role in the clinical practice in order to tailor the best treatment for advanced non-small lung cancer patients (NSCLC). Deeply understanding the molecular mechanisms of NSCLC is very important to the development of new drugs and biomarkers through inhibiting driver mutations responsible for disease pathogenesis. Thus, we believe that this Special Issue will be important to publish the latest updated research in NSCLC regarding future trends in prognostic and predictive biomarkers to help oncologists in the provision of the best care. All types of articles will be considered, such as narrative reviews, meta-analyses, original articles, commentaries and editorials.

Prof. Dr. Ramon Andrade De Mello
Guest Editor

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Keywords

  • TIM3
  • Lung cancer
  • Targeted therapies
  • Immunetherapy
  • Predictive biomarkers
  • Prognostic biomarkers

Published Papers (12 papers)

2023

Jump to: 2022, 2021, 2020

12 pages, 679 KiB  
Review
The Early Diagnosis of Lung Cancer: Critical Gaps in the Discovery of Biomarkers
by Roberto Gasparri, Angela Sabalic and Lorenzo Spaggiari
J. Clin. Med. 2023, 12(23), 7244; https://doi.org/10.3390/jcm12237244 - 23 Nov 2023
Viewed by 1560
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide. The main issue is the absence of a screening test available in clinical practice; the identification of noninvasive biomarkers is thus an urgent clinical necessity. Currently, low-dose computed tomography (LD-CT) demonstrates a 20% [...] Read more.
Lung cancer remains the leading cause of cancer-related mortality worldwide. The main issue is the absence of a screening test available in clinical practice; the identification of noninvasive biomarkers is thus an urgent clinical necessity. Currently, low-dose computed tomography (LD-CT) demonstrates a 20% reduction in lung cancer mortality. However, it is not particularly suitable for clinical practice because of its costs, radiation, and false-positive rate. Several studies have therefore focused on research into biomarkers in body fluids. Despite the power of certain molecules to distinguish lung cancer patients from healthy subjects, no biomarker has yet been shown to significantly and reliably influence clinical decisions or to be translated from the laboratory to clinical practice. In this paper, we provide an overview of the peer-reviewed biomedical literature published in the last 10 years on the research regarding biomarkers for the early diagnosis of lung cancer via a comprehensive analysis of the reviews published this past year. Our main objective is to highlight the limitations and strengths of studies on predictive lung cancer biomarkers to stimulate further investigation for early diagnosis. Finally, we discuss future perspectives on managing clinical trials for biomarker research and their integration into clinical practice. Full article
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2022

Jump to: 2023, 2021, 2020

11 pages, 2143 KiB  
Article
Profiling Plasma Cytokines by A CRISPR-ELISA Assay for Early Detection of Lung Cancer
by Ning Li, Molangur Chinthalapally, Van K. Holden, Janaki Deepak, Pushpa Dhilipkannah, Jonathan M. Fan, Nevins W. Todd and Feng Jiang
J. Clin. Med. 2022, 11(23), 6923; https://doi.org/10.3390/jcm11236923 - 24 Nov 2022
Cited by 2 | Viewed by 1928
Abstract
Cytokines play crucial roles in tumorigenesis and are potential biomarkers for cancer diagnosis. An Enzyme-linked Immunosorbent Assay (ELISA) is commonly used to measure cytokines but has a low sensitivity and can only detect a single target at a time. CRISPR-Associated Proteins (Cas) can [...] Read more.
Cytokines play crucial roles in tumorigenesis and are potential biomarkers for cancer diagnosis. An Enzyme-linked Immunosorbent Assay (ELISA) is commonly used to measure cytokines but has a low sensitivity and can only detect a single target at a time. CRISPR-Associated Proteins (Cas) can ultra-sensitively and specifically detect nucleic acids and is revolutionizing molecular diagnostics. Here, we design a microplate-based CRISPR-ELISA assay to simultaneously profile multiple cytokines, in which antibodies are coupled with ssDNA to form antibody-ssDNA complexes that bridges CRISPR/Cas12a and ELISA reactions. The ssDNA triggers the Cas12a collateral cleavage activity and releases the fluorescent reporters to generate amplified fluorescent signals in the ELISA detection of cytokines. The CRISPR-ELISA assay can simultaneously measure multiple cytokines with a significantly higher sensitivity compared with conventional ELISA. Using the CRISPR-ELISA assay to profile plasma cytokines in 127 lung cancer patients and 125 cancer-free smokers, we develop a panel of plasma cytokine biomarkers (IL-6, IL-8, and IL-10) for early detection of the disease, with 80.6% sensitivity and 82.0% specificity. The CRISPR-ELISA assay may provide a new approach to the discovery of cytokine biomarkers for early lung cancer detection. Full article
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13 pages, 1400 KiB  
Article
Small Cell Lung Cancer Transformation following Treatment in EGFR-Mutated Non-Small Cell Lung Cancer
by Isa Mambetsariev, Leonidas Arvanitis, Jeremy Fricke, Rebecca Pharaon, Angel R. Baroz, Michelle Afkhami, Marianna Koczywas, Erminia Massarelli and Ravi Salgia
J. Clin. Med. 2022, 11(5), 1429; https://doi.org/10.3390/jcm11051429 - 5 Mar 2022
Cited by 13 | Viewed by 3360
Abstract
EGFR-mutated lung adenocarcinoma patients who received tyrosine kinase inhibitors (TKIs) may initially respond to therapy, but over time, resistance eventually occurs. In a small population (5–10%), these patients can have a histological transformation to SCLC. Nine patients with EGFR-mutated lung adenocarcinoma who transformed [...] Read more.
EGFR-mutated lung adenocarcinoma patients who received tyrosine kinase inhibitors (TKIs) may initially respond to therapy, but over time, resistance eventually occurs. In a small population (5–10%), these patients can have a histological transformation to SCLC. Nine patients with EGFR-mutated lung adenocarcinoma who transformed to SCLC were evaluated at City of Hope. Patient clinical and pathology data, including multiple next-generation sequencing (NGS) results, clinical therapies, histology, and outcomes, were collected across multiple time points. Descriptive statistics were utilized to visualize and interpret the clinical therapeutic timeline and molecular transformation profiles for these patients. All patients received at least one line of EGFR TKI therapies prior to small cell lung cancer transformation, including erlotinib, afatinib, and osimertinib. Two patients also received chemotherapy prior to transformation (one with immunotherapy). The median months to small cell lung cancer transformation was 16 months, ranging from 4–49 months. The median overall survival (OS) was 29 months from diagnosis, with the minimum of 16 months and maximum of 62 months. The majority of patients had EGFR exon 19 deletion (n = 7, 77.8%), and no patients had a change of original oncogenic EGFR mutation over the different time points. Though a TP53 mutation was detected in eight patients (88.9%) either at the first biopsy or the subsequent biopsies, an RB1 alteration was only detected in one patient at presentation, and three patients upon subsequent biopsies (n = 4, 44.4%). Each patient had a unique molecular profile in the subsequent molecular testing post-transformation, but BRAF alterations occurred frequently, including BRAF rearrangement (n = 1), fusion (n = 1), and amplification (n = 1). Our results showed that EGFR-mutated lung adenocarcinoma to SCLC transformation patients have a unique histological, molecular, and clinical profile over multiple time points, with further heterogeneity that is not currently reported in the literature, and we suggest more work is required to better understand the molecular heterogeneity and clinical outcomes over time for this EGFR TKI resistance subtype. Full article
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13 pages, 1549 KiB  
Article
Clinical Utility of Plasma Cell-Free DNA EGFR Mutation Analysis in Treatment-Naïve Stage IV Non-Small Cell Lung Cancer Patients
by Bo-Guen Kim, Ja-Hyun Jang, Jong-Won Kim, Sun Hye Shin, Byeong-Ho Jeong, Kyungjong Lee, Hojoong Kim, O Jung Kwon, Myung-Ju Ahn and Sang-Won Um
J. Clin. Med. 2022, 11(4), 1144; https://doi.org/10.3390/jcm11041144 - 21 Feb 2022
Cited by 3 | Viewed by 1930
Abstract
Background: Plasma cell-free Deoxyribo nucleic acid epidermal growth factor receptor (EGFR) mutation tests are widely used at initial diagnosis and at progression in stage IV non-small cell lung cancer (NSCLC). We analyzed the factors associated with plasma EGFR mutation detection and the effect [...] Read more.
Background: Plasma cell-free Deoxyribo nucleic acid epidermal growth factor receptor (EGFR) mutation tests are widely used at initial diagnosis and at progression in stage IV non-small cell lung cancer (NSCLC). We analyzed the factors associated with plasma EGFR mutation detection and the effect of plasma EGFR genotyping on the clinical outcomes of the patients with treatment-naïve stage IV NSCLC. Methods: In this retrospective cohort study, we included subjects with treatment-naïve stage IV NSCLC who underwent plasma EGFR genotyping between 2018 and 2020. The presence of plasma EGFR mutation was determined by real-time polymeric chain reaction. Results: The prevalence of EGFR mutation in this cohort was 52.7% (164/311). Among 164 EGFR mutant subjects, 34 (20.7%) were positive for the plasma EGFR mutation assay only. In multivariable analysis, the detection of plasma EGFR mutation was significantly related to higher serum carcinoembryonic antigen levels, never-smoker status, N3 stage, and brain or intrathoracic metastasis. The time to treatment initiation (TTI) of the plasma EGFR mutation-positive group (14 days) was shorter than that of the plasma EGFR mutation-negative group (21 days, p < 0.001). More patients received the 1st line EGFR-TKI in the plasma positive group compared with the tissue positive group. Conclusion: Smoking status and the factors reflecting tumor burden were associated with the detection of plasma EGFR mutation. The plasma EGFR mutation assay can shorten the TTI, and facilitate the 1st line EGFR-TKI therapy for patients with treatment-naïve stage IV NSCLC, especially in the region of high-prevalence of EGFR mutation. Full article
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15 pages, 959 KiB  
Article
The Significance of the Alter miR let-7a and miR-335 Expression Level Regulating the CCR7/CCL19 Axis as Potential Biomarkers of Tumor Progression in NSCLC
by Kamila Baran, Jacek Kordiak, Sławomir Jabłoński, Adam Antczak and Ewa Brzeziańska-Lasota
J. Clin. Med. 2022, 11(3), 655; https://doi.org/10.3390/jcm11030655 - 27 Jan 2022
Cited by 5 | Viewed by 1678
Abstract
The chemokine receptor 7/C-C ligand 19 chemokine (CCR7/CCL19) has been implicated in the development and progression of NSCLC. Its expression is regulated by various epigenetic factors including miRNAs. The aim of this study was to assess the expression of CCR7/CCL19 in cancer tissue [...] Read more.
The chemokine receptor 7/C-C ligand 19 chemokine (CCR7/CCL19) has been implicated in the development and progression of NSCLC. Its expression is regulated by various epigenetic factors including miRNAs. The aim of this study was to assess the expression of CCR7/CCL19 in cancer tissue in relation to that of miRNAs (miR-let-7a, miR-335) as transcriptional regulators. The expression of the tested miRNAs was also evaluated in serum exosomes. Sixty patients (n = 60) were enrolled in the study. The total expression of the studied mRNA and miRNAs were evaluated using qPCR. Tumor tissue fragments, macroscopically unchanged adjacent tissue, and serum were used as controls. Higher CCR7 and CCL19 mRNA expression levels were observed in tumor tissue compared to control. According to stages of the disease (AJCC tumor staging), the greatest expression level of the studied genes’ mRNA was observed in patients with stage III. In NSCLC patients, lower miR let-7a expression level was observed in tumor tissue compared to serum; however, miR-335 expression level was higher (p < 0.05). The expression level of miR-335 positively correlated with tumor size (T features according to pTNM staging) and AJCC tumor staging, while miR let-7a had a negative correlation (p > 0.05) with liquid biopsy. Significantly greater miR-335 expression level and lower miR let-7a expression level in serum were observed in patients with metastases to lymph nodes. Our findings reveal a significant correlation between the expression levels of the mRNA of the studied genes and miRNAs. Changes in miR-335 and miR let-7a expression levels in the serum exosomes of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression. Full article
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2021

Jump to: 2023, 2022, 2020

14 pages, 3161 KiB  
Review
PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis
by María Rosario García Campelo, Edurne Arriola, Begoña Campos Balea, Marta López-Brea, José Fuentes-Pradera, Javier de Castro Carpeno, Carlos Aguado, Diego Pérez Parente, Fidel de Oro Pulido, Pedro Ruiz-Gracia and Delvys Rodríguez-Abreu
J. Clin. Med. 2021, 10(19), 4583; https://doi.org/10.3390/jcm10194583 - 4 Oct 2021
Cited by 3 | Viewed by 2674
Abstract
This network meta-analysis (NMA) evaluates the safety of first-line programmed death-ligand 1 (PD-L1) inhibitor monotherapy in advanced NSCLC patients compared to platinum-based chemotherapy. We also compared the risk of adverse events (AEs) according to programmed cell death-1 receptor (PD-1) or PD-L1 inhibitors therapy. [...] Read more.
This network meta-analysis (NMA) evaluates the safety of first-line programmed death-ligand 1 (PD-L1) inhibitor monotherapy in advanced NSCLC patients compared to platinum-based chemotherapy. We also compared the risk of adverse events (AEs) according to programmed cell death-1 receptor (PD-1) or PD-L1 inhibitors therapy. To that end, we conducted a series of metanalyses (MAs) using data from six phase III clinical trials, including 4053 patients. Our results show a reduced risk of any grade treatment-related AEs (risk ratio (RR) = 0.722 95% CI: 0.667–0.783, p = 0.002), and grade 3–5 AEs (RR = 0.406 95% CI: 0.340–0.485, p = 0.023) in immunotherapy as compared to chemotherapy. In contrast, a higher risk of immune-related AEs (irAEs) was estimated for immunotherapy versus chemotherapy. The subgroup MAs comparing PD-L1 to PD-1 inhibitors, determined a lower risk of AEs leading to treatment discontinuation in the anti-PD-L1 subgroup (RR = 0.47 95% CI: 0.29–0.75, p = 0.001); however, this statistically significant difference between anti-PD-L1 and anti-PD-1 subgroups was not reached for other safety outcomes analyzed. In conclusion, our findings show that PD-L1 inhibitor monotherapy improves safety outcomes in the 1L treatment of advanced NSCLC patients as compared to chemotherapy except for irAEs. Full article
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11 pages, 2277 KiB  
Article
Decreased Thrombospondin-1 and Bone Morphogenetic Protein-4 Serum Levels as Potential Indices of Advanced Stage Lung Cancer
by Monika Kosacka, Tomasz Dyła, Monika Chaszczewska-Markowska, Katarzyna Bogunia-Kubik and Anna Brzecka
J. Clin. Med. 2021, 10(17), 3859; https://doi.org/10.3390/jcm10173859 - 27 Aug 2021
Cited by 4 | Viewed by 1875
Abstract
Introduction: Lung cancer belongs to the most common carcinoma worldwide and is the leading cause of cancer-related death. Bone morphogenetic protein-4 (BMP-4) is extracellular signaling molecule involved in many important processes, including cell proliferation and mobility, apoptosis and angiogenesis. Thrombospondin-1 (TSP-1) belongs to [...] Read more.
Introduction: Lung cancer belongs to the most common carcinoma worldwide and is the leading cause of cancer-related death. Bone morphogenetic protein-4 (BMP-4) is extracellular signaling molecule involved in many important processes, including cell proliferation and mobility, apoptosis and angiogenesis. Thrombospondin-1 (TSP-1) belongs to the extracellular matrix proteins. It participates in the cell-to-cell and cell-to-matrix interactions and thus plays important role in tumor microenvironment for cancer development and metastasis formation. Aim: To investigate serum levels of TSP-1 and BMP-4 together with BMP-4 polymorphism in lung cancer patients. Material and Methods: A total of 111 patients (76 men) with newly diagnosed lung cancer, including 102 patients with non-small cell lung cancer and 9 patients with small-cell lung cancer. Advanced stage of lung cancer was diagnosed in 99 (89%) of patients: stage IV—in 48, stage IIIB—in 33, stage IIIA—in 18 patients; there were six patients with stage II and six patients with stage I. The control group consisted of 61 healthy persons. In all the subjects, serum levels of BMP-4 and TSP-1 were measured by ELISA. With a Real-Time PCR system genotyping of BMP-4 was performed. Results: BMP-4 and TSP-1 serum levels were significantly lower in the patients with lung cancer than in the controls (TSP-1:10,109.2 ± 9581 ng/mL vs. 11,415.09 ± 9781 ng/mL, p < 0.05; BMP-4: 138.35 ± 62.59 pg/mL vs. 226.68 ± 135.86 pg/mL p < 0.001). In lung cancer patients TSP-1 levels were lower in advanced stages (9282.07 ± 4900.78 ng/mL in the stages III-IV vs. 16,933.60 ± 6299.02 ng/mL in the stages I-II, p < 0.05) and in the patients with than without lymph nodes involvement (10,000.13 ± 9021.41 ng/mL vs. 18,497.75 ± 12,548.25 ng/mL, p = 0.01). There was no correlation between TSP-1 and BMP-4 serum levels. BMP-4 gene polymorphism did not influence the results of the study. Conclusion: Decreased levels of TSP-1 and BMP-4 may serve as potential indices of lung cancer, with additional importance of low TSP-1 level as a marker of advanced stage of the disease. Full article
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16 pages, 759 KiB  
Review
PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis
by Margarita Majem, Manuel Cobo, Dolores Isla, Diego Marquez-Medina, Delvys Rodriguez-Abreu, Joaquín Casal-Rubio, Teresa Moran-Bueno, Reyes Bernabé-Caro, Diego Pérez-Parente, Pedro Ruiz-Gracia, Marta Marina Arroyo and Luis Paz-Ares
J. Clin. Med. 2021, 10(7), 1365; https://doi.org/10.3390/jcm10071365 - 26 Mar 2021
Cited by 13 | Viewed by 5445
Abstract
Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of [...] Read more.
Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug. Full article
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2020

Jump to: 2023, 2022, 2021

16 pages, 266 KiB  
Review
Club Cell Secreted Protein CC16: Potential Applications in Prognosis and Therapy for Pulmonary Diseases
by Sultan Almuntashiri, Yin Zhu, Yohan Han, Xiaoyun Wang, Payaningal R. Somanath and Duo Zhang
J. Clin. Med. 2020, 9(12), 4039; https://doi.org/10.3390/jcm9124039 - 14 Dec 2020
Cited by 48 | Viewed by 5053
Abstract
Club cell secretory protein (CC16) is encoded by the SCGB1A1 gene. It is also known as CC10, secretoglobin, or uteroglobin. CC16 is a 16 kDa homodimeric protein secreted primarily by the non-ciliated bronchial epithelial cells, which can be detected in the airways, circulation, [...] Read more.
Club cell secretory protein (CC16) is encoded by the SCGB1A1 gene. It is also known as CC10, secretoglobin, or uteroglobin. CC16 is a 16 kDa homodimeric protein secreted primarily by the non-ciliated bronchial epithelial cells, which can be detected in the airways, circulation, sputum, nasal fluid, and urine. The biological activities of CC16 and its pathways have not been completely understood, but many studies suggest that CC16 has anti-inflammatory and anti-oxidative effects. The human CC16 gene is located on chromosome 11, p12-q13, where several regulatory genes of allergy and inflammation exist. Studies reveal that factors such as gender, age, obesity, renal function, diurnal variation, and exercise regulate CC16 levels in circulation. Current findings indicate CC16 not only may reflect the pathogenesis of pulmonary diseases, but also could serve as a potential biomarker in several lung diseases and a promising treatment for chronic obstructive pulmonary disease (COPD). In this review, we summarize our current understanding of CC16 in pulmonary diseases. Full article
20 pages, 1072 KiB  
Review
New Target Therapies in Advanced Non-Small Cell Lung Cancer: A Review of the Literature and Future Perspectives
by Ramon Andrade de Mello, Nathália Moisés Neves, Hakaru Tadokoro, Giovanna Araújo Amaral, Pedro Castelo-Branco and Victor André de Almeida Zia
J. Clin. Med. 2020, 9(11), 3543; https://doi.org/10.3390/jcm9113543 - 3 Nov 2020
Cited by 30 | Viewed by 8090
Abstract
Introduction: Lung cancer (LC) is the most common neoplasm worldwide, and 85% of these tumors are classified as non-small cell lung cancer (NSCLC). LC treatment was initially restricted to cytotoxic chemotherapy—platinum compounds associated with 3rd generation cytotoxic agents (paclitaxel, gemcitabine, pemetrexed) and, more [...] Read more.
Introduction: Lung cancer (LC) is the most common neoplasm worldwide, and 85% of these tumors are classified as non-small cell lung cancer (NSCLC). LC treatment was initially restricted to cytotoxic chemotherapy—platinum compounds associated with 3rd generation cytotoxic agents (paclitaxel, gemcitabine, pemetrexed) and, more recently, with monoclonal antibodies (bevacizumab, ramucirumab). Advancements in treatment are correlated with prolonged overall survival (OS). Current advances are focused on target therapies. Target agents: Anti-epidermal growth factor receptor (EGFR) therapy consists of 1st and 2nd generation tyrosine kinase inhibitors (TKIs such as erlotinib, afatinib). In 60% of cases, resistance to these TKIs occurs due to T790M mutation in EGFR, which is overcome 3rd generation drugs (osimertinib). Anaplastic lymphoma kinase (ALK) is the target for drugs such as crizotinib, alectinib, ceritinib. Programmed death 1 (PD-1) and its ligand serve as targets for immunotherapy agents such as pembrolizumab, nivolumab, atezolizumab. Discussion: Challenges in NSCLC treatment include resistance to 3rd generation TKIs, the high cost of ALK inhibitors, and the need for further research on new drugs. Full article
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3 pages, 194 KiB  
Editorial
Biomarkers for Non-Small Cell Lung Cancer: From the Bench to the Bedside
by Ramon Andrade de Mello and Giovanna Araújo Amaral
J. Clin. Med. 2020, 9(10), 3376; https://doi.org/10.3390/jcm9103376 - 21 Oct 2020
Cited by 2 | Viewed by 1648
Abstract
Lung cancer (LC) is inarguably one of the biggest battles to be fought in the field of oncology, and non-small cell lung cancer accounts for over 85% of all lung cancer cases [...] Full article
16 pages, 480 KiB  
Review
The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer
by Ramon Andrade De Mello, Nathália Moisés Neves, Giovanna Araújo Amaral, Estela Gudin Lippo, Pedro Castelo-Branco, Daniel Humberto Pozza, Carla Chizuru Tajima and Georgios Antoniou
J. Clin. Med. 2020, 9(6), 1918; https://doi.org/10.3390/jcm9061918 - 19 Jun 2020
Cited by 18 | Viewed by 3996
Abstract
Introduction: Non-small cell lung cancer (NSCLC) is the second most common cancer globally. The mesenchymal-epithelial transition (MET) proto-oncogene can be targeted in NSCLC patients. Methods: We performed a literature search on PubMed in December 2019 for studies on MET inhibitors and [...] Read more.
Introduction: Non-small cell lung cancer (NSCLC) is the second most common cancer globally. The mesenchymal-epithelial transition (MET) proto-oncogene can be targeted in NSCLC patients. Methods: We performed a literature search on PubMed in December 2019 for studies on MET inhibitors and NSCLC. Phase II and III clinical trials published in English between 2014 and 2019 were selected. Results: Data on MET inhibitors (tivantinib, cabozantinib, and crizotinib) and anti-MET antibodies (emibetuzumab and onartuzumab) are reported in the text. Conclusion: Emibetuzumab could be used for NSCLC cases with high MET expression. Further, studies on onartuzumab failed to prove its efficacy, while the results of tivantinib trials were clinically but not statistically significant. Additionally, cabozantinib was effective, but adverse reactions were common, and crizotinib was generally well-tolerated. Full article
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