Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure–activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties. READ ARTICLE

Acta Pharmaceutica Sinica B DOI: 10.1016/j.apsb.2020.07.010

Authors: Zhendong Song, Meijing Wang, Yang Ge, Xue-Ping Chen, Ziyang Xu, Yang Sun, Xiao-Feng Xiong

Review PaperKirk SmithJuly 15, 2020SHP2, Phosphatase, Selectivity, Allosteric inhibitor, Tumor therapy

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Summary: To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification ..... READ ARTICLE

Cell DOI:10.1016/j.cell.2020.06.013

Authors: Michael A. Gillette, Shankha Satpathy, Song, Cao,.. AND MANY MORE

Continual Improvement of the Reliability of EML4-ALK Rearrangement Detection in Non–Small-Cell Lung Cancer: A Long-Term Comparison of ALK Detection in China

The results of EML4-ALK testing are critical to manage ALK tyrosine kinase receptor inhibitor treatment. Thus, the accurate detection of ALK rearrangement is increasingly becoming a matter of serious concern. To address this issue, a long-term EML4-ALK proficiency testing (PT) scheme was launched in China in 2015, serving as an educational tool for assessing and improving the testing quality of EML4-ALK fusion detection. Responses across 20 different PT samples interrogating three different variants and wild-type samples were collected between 2015 and 2019. Performance was analyzed by evaluating the detection methods, kits, and pre-analytic practices used to further display the landscape of changing conditions of the reliability of EML4-ALK testing... Throughout this 5-year EML4-ALK rearrangement detection PT scheme, a large amount of valuable historical data was collected. As it is of interest to investigate whether the performance of EML4-ALK rearrangement tests has changed over th..... READ ARTICLE

The Journal of Molecular Diagnostics DOI:10.1016/j.jmoldx.2020.03.007

Authors: Rongxue Peng, Rui Zhang, Jiawei Zhang, Ping Tan, Yanxi Han, Kuo Zhang, Guigao Lin, Jiehong Xie, Jinming Li

A Comprehensive Review of Clinical Cardiotoxicity Incidence of FDA-Approved Small-Molecule Kinase Inhibitors

Numerous protein kinases encoded in the genome have become attractive targets for the treatment of different types of cancer. As of January 2020, a total of 52 small-molecule kinase inhibitors (SMKIs) have been approved by the FDA. With the numerous clinical trials and a heavy focus on drug safety, SMKI-induced cardiotoxicity, which is a life-threatening risk, has greatly attracted the attention of researchers. In this review, the SMKIs with cardiotoxicity incidence were described exhaustively. The data were collected from 42 clinical trials, 25 FDA-published documents, seven meta-analysis/systematic reviews, three case reports and more than 50 other types of articles. To date, 73% (38 of 52) of SMKIs have reported treatment-related cardiotoxicity. Among the 38 SMKIs with known cardiotoxicity, the rates of incidence of cardiac adverse events were QT prolongation: 47% (18 of 38), hypertension: 40% (15 of 38), left ventricular dysfunction: 34% (13 of 38), arrhythmia: 34% (13 of 38), heart failure: 26% (10 of 38) and ischemia or myocardial infarction: 29% (11 of 38). In the development process of novel SMKIs, more attention should be paid to balancing the treatment efficacy and the risk of cardiotoxicity. In preclinical drug studies, producing an accurate and reliable cardiotoxicity evaluation model is of key importance. To avoid the clinical potential cardiotoxicity risk and discontinuation of a highly effective drug, patients treated with SMKIs should be proactively monitored on the basis of a global standard. Moreover, the underlying mechanisms of SMKI-induced cardiotoxicity need to be further studied to develop new therapies for SMKI-induced cardiotoxicity. READ ARTICLE

Frontiers in Pharmacology DOI:10.3389/fphar.2020.00891

Authors: Ying Jin, Zhifei Xu, Hao Yan, Qiaojun He, Xiaochun Yang, and Peihua Luo

Going beneath the tip of the iceberg. Identifying and understanding EML4-ALK variants and TP53 mutations to optimize treatment of ALK fusion positive (ALK+) NSCLC

More than 10 EML4-ALK variants based on the exon breakpoints in EML4 have been identified. Unlike other receptor tyrosine kinase fusion positive NSCLC such as ROS1 or RET fusion, EML4-ALK is the dominant fusion variant in ALK+ NSCLC accounting for approximately 85 % of all fusion variants in ALK+ NSCLC. Currently, eight EML4-ALK variants are generally recognized with a number (1, 2, 3a/b, 4′, 5a/b, 5′, 7, 8) with EML4-ALK variants 1 and 3 being the two most common variants accounting for 75–80 % of the total EML4-ALK variants. Preclinical, retrospective analyses of institutional databases, and global randomized phase 3 trials have demonstrated differential clinical response (overall response rate, progression-free survival) to ALK tyrosine kinase inhibitors (TKIs) between the “short” (v3 and v5) and “long” (v1, v2, v5′, v7, and v8) EML4-ALK variants. We discuss in more details how EML4-ALK variant structure influences protein stability and response to ALK TKIs. Additionally, the most recalcitrant single solvent-front mutation ALK G1202R is more prone to develop among EML4-ALK v3 following sequential use of next-generation ALK TKIs. Furthermore, TP53 mutations being the most common genomic co-alterations in ALK+ NSCLC also contribute to the heterogeneous response to ALK TKIs. Recognizing ALK+ NSCLC is not one homogeneous disease entity but comprised of different ALK fusion variants with different underlying genomic alterations in particular TP53 mutations that modulate treatment response will provide insight into the further optimization of treatment of ALK+ NSCLC patients potentially leading to improvement in survival. READ ARTICLE

Lung cancer DOI: 10.1016/j.lungcan.2021.06.012

Authors: Shannon S. Zhang, Misako Nagasaka, Viola W. Zhu, Sai-Hong Ignatius Ou

Optimizing Mutation and Fusion Detection in NSCLC by Sequential DNA and RNA Sequencing

Introduction: Frequently, patients with locally advanced or metastatic NSCLC are screened for mutations and fusions. In most laboratories, molecular workup includes a multitude of tests: immunohistochemistry (ALK, ROS1, and programmed death-ligand 1 testing), DNA sequencing, in situ hybridization for fusion, and amplification detection. With the fast-emerging new drugs targeting specific fusions and exon-skipping events, this procedure harbors a growing risk of tissue exhaustion... Conclusions: We conclude that sequentially combining DNA NGS and RNA NGS is the most efficient strategy for mutation and fusion detection in smoking-associated NSCLC, whereas for never smokers we recommend a parallel approach. This approach was shown to be feasible on small tissue samples including for cytology tests, can drastically reduce the complexity and cost of molecular workup, and also provides flexibility in the constantly evolving landscape of actionable targets in NSCLC. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.01.019

Authors: Danielle Cohen, Liesbeth M. Hondelink, Nienke Solleveld-Westerink, Sandra M. Uljee, Dina Ruano, Anne-Marie Cleton-Jansen, Jan H. von der Thüsen, S. Rajen S. Ramai, Pieter E. Postmus, Jacob F. Graadt van Roggen, Bart P. C. Hoppe, Pieter C. Clahsen, Klaartje W. Maas, Els J. M. Ahsmann, Alexandraten Heuvel, Frank Smedts, Ronald N. van Rossem,Tomvan Wezel

Acquired resistance to targeted therapies in NSCLC: Updates and evolving insights

While significant advancements have been made in the available therapies for metastatic non-small cell lung cancer (NSCLC), acquired resistance remains a major barrier to treatment. We have not yet achieved the ability to cure advanced NSCLC with systemic therapy, despite our growing understanding of many of the oncogenic drivers of this disease. Rather, the emergence of drug-tolerant and drug-resistant cells remains the rule, even in the face of increasingly potent targeted therapies. In this review, we provide a broad overview of the mechanisms of resistance to targeted therapy that have been demonstrated across molecular subtypes of NSCLC, highlighting the dynamic interplay between driver oncogene, bypass signaling pathways, shifting cellular phenotypes, and surrounding tumor microenvironment. READ ARTICLE

Pharmacology & Therapeutics DOI:10.1016/j.pharmthera.2020.107522

Authors: Catherine B. Meador, Aaron N. Hata

Efficacy and safety of ALK inhibitors in ALK-rearranged non-small cell lung cancer: A systematic review and meta-analysis

Objectives: No overall survival (OS) benefit has been reported from a mature randomized trial with the use of ALK inhibitors. We conducted a systematic review and meta-analysis to assess the efficacy of ALK inhibitors compared to chemotherapy (ALK vs. chemo) and 2nd generation ALK inhibitors compared to 1 st generation ALK inhibitors (ALK-2 G vs. ALK-1 G)... Conclusions: This meta-analysis is the first, to our knowledge, to report an OS and PFS benefit with the use of ALK inhibitors compared to chemotherapy from randomized trial data. A trend toward a better OS was also seen with ALK-2 G vs. ALK-1 G and this is likely because of crossover effects and limited OS follow-up. Longer follow up and further research are warranted to directly compare ALK inhibitor sequences and to understand the outcomes of second generation ALK inhibitors as initial therapy. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.04.011

Authors: Daniel Breadner, Phillip Blanchette, Sumugan Shanmuganathan, Ronald Gabriel Boldt, Jacques Raphael

Anaplastic lymphoma kinase (ALK) partners identified by next-generation sequencing in Chinese patients with solid tumors

Background: Anaplastic lymphoma kinase (ALK) rearrangement is a validated therapeutic driver gene in non-small cell lung cancer (NSCLC). More than 30 different fusion partner genes of ALK in NSCLC have been reportedand most of these ALK fusions respond well to ALK inhibitors crizotinib. With the development of next-generation sequencing (NGS), more novel partners for ALK rearrangement have been identified. Here, we aimed to report the landscape of ALK rearrangement in Chinese patients with solid tumors... Conclusions: Novel ALK fusions are detected in patients with not only NSCLC but also other solid tumors. NGS fusion assay is an optional method for screening novel fusions. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.3555

Authors: Sheng Yang, Fuyu Gong, Guoqiang Wang, Xiaohui He

A multicenter real-world study of tumor-derived DNA from pleural effusion supernatant in genomic profiling of advanced lung cancer

Background: Pleural effusion (PE) is commonly observed in advanced lung cancer. Researches have suggested molecular profiling of PE represents a minimally invasive approach of detecting tumor driver mutations for clinical decision making. The objective of this study is to investigate the efficacy and precision of detecting gene alterations in PE samples in the real world setting... Conclusions: This real world large cohort study verified that genomic profiling of PE-supernatant has higher actionable mutation detection sensitivity than plasma. It offers an alternative approach in assessing tumor genomics in advanced lung cancer when tumor tissue is not available. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.e21584

Authors: Renhua Guo, Likun Chen, Chengzhi Zhou, Xinghao Ai, Jun Zhao, Rongrong Chen, Xuefeng Xia

Longitudinal monitoring by next generation sequencing of plasma cell-free DNA in ALK-rearranged non-small cell lung cancer (NSCLC) patients treated with ALK tyrosine kinase inhibitors

Background: Patients with anaplastic lymphoma kinase-rearranged (ALK+) NSCLC inevitably acquire resistance to ALK inhibitors. We hypothesized that longitudinal monitoring of cell-free plasma DNA (cfDNA) next generation sequencing (NGS) could predict the response and resistance of TKI therapy in ALK+NSCLC... Conclusions: NGS of cell-free plasma DNA is useful not only for the detection of ALK fusions and resistance mutations but also for assessing prognosis and monitoring the dynamic changes of genomic alterations in ALK+ NSCLC treated with ALK TKI. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.9603

Authors: Minsuk Kwon, Bo Mi Ku, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn

Clinical impact of targetable gene alterations on therapeutic outcomes in stage II/III locally advanced non-small cell lung cancer patients

Background: The clinical significance of genetic alterations in stage II/III non-small cell lung cancer (NSCLC) patients has not yet been clarified. We have prospectively analyzed NSCLC patients for cancer-related gene alterations and have followed up clinical course of the patients, establishing a large-scale clinico-genomic database in our nationwide genome screening project (LC-SCRUM-Japan)... Conclusions: In stage II/III NSCLC, the total frequency of targetable gene alterations was similar to that previously evaluated in our stage IV cohort (45%), and the current standard therapies showed early progression in the targetable gene-altered patients. A novel effective multimodality treatment in combination with targeted therapies is needed for this population. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.9038

Authors: Yoshitaka Zenke, Shingo Matsumoto, Terufumi Kato, Shingo Miyamoto, Takuma Imakita, Tetsuya Mitsudomi, Hiromi Aono, Ryota Ushio, Naoki Furuya, Kazumi Nishino, Saori Takata, Mika Nakao, Satoshi Hara, Motoko Tachihara, Akimasa Sekine, Jun Sakakibara-Konishi, Ryo Toyozawa, Kiyotaka Yoh, Koichi Goto

Review PaperKirk SmithMay 25, 2020Gene alterations, non-small cell lung cancer

Population pharmacokinetic (PK) and exposure-response analyses from the pivotal ALTA-1L study: Model-based analyses supporting the brigatinib dose...

Background: Brigatinib is a next-generation ALK tyrosine kinase inhibitor (TKI) with differential activity by dose (90 mg vs 180 mg [with a 7-day lead-in at 90 mg] qd) in the phase 2 post-crizotinib ALTA trial (NCT02094573). Herein, we describe results from population PK and exposure-response analyses of the efficacy and safety of brigatinib 180 mg qd (with a 7-day lead-in at 90 mg) from data in the first-line phase 3 ALTA-1L study (NCT02737501)... Conclusions: These results support a favorable benefit/risk profile of the proposed 180 mg qd brigatinib dose (with a 7-day lead-in at 90 mg) for the front-line treatment of patients with ALK+ NSCLC. Clinical trial information: NCT02737501. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.e21725

Authors: Neeraj Gupta, Karen L. Reckamp, D. Ross Camidge, Huub Jan Kleijn, Aziz Ouerdani, Francesco Bellanti, John Maringwa, Michael J. Hanley, Shining Wang, Pingkuan Zhang, Karthik Venkatakrishnan

Lorlatinib for advanced ALK and ROS1+ non-small cell lung cancer (NSCLC): Efficacy and treatment sequences in the IFCT-1803 LORLATU expanded access program (EAP) cohort

Background: Lorlatinib, a third-generation tyrosine kinase inhibitor targeting ALK and ROS1, has been made available in France starting October 2015 through an EAP for advanced, refractory, ALK+ NSCLC after the failure of chemotherapy and TKIs. Besides the landmark, multi-cohort phase II trial that assessed lorlatinib in ALK+ NSCLC, real-life evidence regarding the efficacy and safety, as well as treatment sequences including lorlatinib, is lacking. Methods: We report the cohort of consecutive patients with advanced, refractory, ALK or ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to October 2019. Data were collected from medical records by French Cooperative Thoracic Intergroup (IFCT) research study assistants on site. Primary endpoint was progression-free survival... Conclusions: These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.9615

Authors: Simon Baldacci, Virginie Avrillon, Benjamin Besse, Bertrand Mennecier, Michael Duruisseaux, Julien Mazieres, Renaud Descourt, Helene Doubre, Pascale Dubray-Longeras, Jacques Cadranel, Denis Moro-Sibilot, Charles Ricordel, Sigolène Galland-Girodet, Isabelle Monnet, Josiane Otto, Sophie Schneider, Pascale Missy, Franck Morin, Virginie Westeel, Nicolas Girard

EML4-ALK Fusion as a Resistance Mechanism to Osimertinib and Its Successful Management With Osimertinib and Alectinib: Case Report and Review of the Literature

As the use of up-front osimertinib for advanced epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer is increasing, it is important to understand the resistance pathways to the drug and subsequent treatment. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2020.05.016

Authors: Ullas Batra, Mansi Sharma, B.P. Amrith, Anurag Mehta, Parveen Jain

Attenuated isolated 3’ signal: A highly challenging therapy relevant ALK FISH pattern in NSCLC

Objectives: ... Our aim was to examine a unique atypical ALK FISH pattern, revealed during a systematic large-scale monitoring, which carries the great risk of misinterpretation, hence may result in loss of patients eligible for targeted therapy... Conclusion: Approximately 5% of the 59 ALK positive cases exhibited atypical attenuated isolated 3′ signal pattern. The immunohistochemistry and AMP-NGS examinations helped to clarify the presence of oncoprotein and the fusion gene, respectively. Our results emphasize the importance of extensive exploration of the genetic background of any unexpected FISH finding to avoid false diagnosis. This enables clinicians to indicate the adequate therapy with higher efficiency for patients suffering from NSCLC. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.03.007

Authors: Gábor Smuk, Gábor Pajor, Károly Szuhai, Hans Morreau, Ildikó Kocsmár, Éva Kocsmár, László Pajor, Béla Kajtár, Veronika Sárosi, Gábor Lotz, Tamás Tornóczky

"Brigatinib and Alectinib for ALK Rearrangement-Positive Advanced Non-Small Cell Lung Cancer with or without Central Nervous System Metastasis: A Systematic Review and Network Meta-Analysis"

To date, no head-to-head trials have compared the e cacy of brigatinib and alectinib
against anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p), ALK-inhibitor-naïve,
advanced non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastasis.
We conducted an indirect treatment comparison (ITC) between brigatinib and alectinib, with crizotinib
as a common comparator, using a Bayesian model with non-informative prior distribution and assessed
the between-study heterogeneity of the studies. The primary e cacy endpoint was progression-free
survival (PFS), and e cacy was ranked using the surface under the cumulative ranking (SUCRA)
curve values. ITC analysis showed that there were no significant di erences in PFS between the
brigatinib and alectinib arms. However, the SUCRA values revealed that alectinib ranked the highest
by e cacy in the overall patient population, whereas brigatinib ranked the highest by e cacy in
the CNS metastasis sub-group. Although there wer..... READ ARTICLE

Cancers DOI:10.3390/cancers12040942

Authors: Koichi Ando, Kaho Akimoto, Hiroki Sato, Ryo Manabe, Yasunari Kishino,
Tetsuya Homma, Sojiro Kusumoto, Toshimitsu Yamaoka , Akihiko Tanaka,
Tohru Ohmori,Hironori Sagara

Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review

Anaplastic lymphoma kinase (ALK) inhibitors are important treatment options
for non-small-cell lung cancer (NSCLC), associated with ALK gene rearrangement. Patients
with ALK gene rearrangement show sensitivity to and benefit clinically from treatment with
ALK tyrosine kinase inhibitors (ALK-TKIs). To date, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, and entrectinib have received approval from the US Food and Drug
Administration and/or the European Medicines Agency for use during the treatment of ALKgene-rearrangement forms of NSCLC. Although the oral route of administration is convenient and results in good compliance among patients, oral administration can be affected by
many factors, such as food, intragastric pH, cytochrome P450 enzymes, transporters, and
p-glycoprotein. These factors can result in increased risks for serious adverse events or can
lead to reduced therapeutic effects of ALK-TKIs. This review characterizes and summarizes
the pharmacokinetic parameters and drug–-drug interactions associated with ALK-TKIs to
provide specific recommendations for oncologists and clinical pharmacists when prescribing
ALK-TKIs READ ARTICLE

Drug Design, Development and Therapy DOI:10.2147/DDDT.S249098

Authors: Dehua Zhao, Jing Chen, Mingming Chu, Xiaoqing Long, Jisheng Wang

Review PaperKirk SmithApril 2, 2020ALK, TKIs, NSCLC, Pharmakinetics, drug–drug interactions

Molecular regulatory network of PD-1/PD-L1 in non-small cell lung cancer

Lung cancer remains the most common cancer and the leading cause of cancer death worldwide. Despite effective chemotherapy and molecular-based therapies, the median and overall survival remains poor. Immune checkpoint inhibitors have changed the treatment landscape for patients with non-small cell lung cancer (NSCLC) by inhibiting negative T cell regulators, including programmed death 1 (PD-1, CD279) and programmed death ligand 1 (PD-L1, also known as B-H1, CD274) inhibitors. Nonetheless, most patients do not respond to these inhibitors. Recently, PD-L1 expression has been demonstrated to influence the anti-tumor efficacy of immune checkpoint inhibitors. However, the mechanisms of PD-L1 regulation are not clearly understood. This review thus aims to summarize the current knowledge and recent developments in the regulatory mechanisms of PD-L1 expression levels and attempts to clarify its latent function in anti-tumor activity, with the goal of guiding better designs for future NSCLC immunotherapies. READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2020.152852

Authors: Lingling Zhu, Jiewei Liu, Li Wang, Danli Yan, Jie Zhou, Wen Li, Dan Pu, Lei Peng, Qinghua Zhou

Review PaperKirk SmithApril 1, 2020

Molecular Profiling for Supernatants and Matched Cell Pellets of Pleural Effusions in Non–Small-Cell Lung Cancer

... Herein, we included 47 advanced non–small-cell lung cancer patients with PE, who had lung cancer driver mutations tested on tumor tissue specimens either at diagnosis or during disease progression. The supernatant and cell pellet of each PE were evaluated for molecular profiles in parallel on an Ion Torrent next-generation sequencing platform... In conclusion, our study indicates that supernatant cfTNA isolated from pleural fluids can be effectively used in clinical practice for molecular analysis by NGS. The Oncomine Lung cfTNA assay allows for detecting extremely low-abundance genomic aberrations in supernatants of pleural effusions, even in cases where corresponding cell pellets or biopsy tissues have failed for the detection. Cell-free supernatants and cell pellets could potentially complement each other and improve the detection rate of somatic genetic variants in pleural effusions. READ ARTICLE

The Journal of Molecular Diagnostics DOI:10.1016/j.jmoldx.2020.01.011

Authors: Chan Xiang, Mingfei Huo, Shengji Ma, Lianying Guo, Ruiying Zhao, Haohua Teng, Jie Zhang, Yuchen Han