Posts tagged NSCLC
A targeted expression panel for classification, gene fusion detection and PD-L1 measurements – Can molecular profiling replace immunohistochemistry in non-small cell lung cancer?
A targeted expression panel for classification, gene fusion detection and PD-L1 measurements – Can molecular profiling replace immunohistochemistry in non-small cell lung cancer?

The histological classification of non-small-cell lung cancer (NSCLC) and identification of possible therapeutic targets are important for disease management. However, as biopsies are often small, with a limited amount of tumor cells, it can be challenging to obtain enough tissue for the needed number of diagnostic immunohistochemical stains and molecular analyses. In this study, we combined a small custom designed targeted expression panel with a commercial fusion transcript assay by which we were able to perform both a histological classification (transcribing the expression of the genes encoding TTF1, Napsin A, CK5/6, and the truncated P63 isoform ΔNp63 (p40) into either adenocarcinoma or squamous cell carcinoma) and an identification of fusion genes involving ALK, RET, and ROS1. The expression panel also included the PD-L1 encoding gene, CD274, in order to evaluate the PD-L1 mRNA potential for identification of patients who will benefit from immune checkpoint inhibitor treatment. We evaluated the panel using 42 NSCLC patient samples. The molecular profiling agreed with the original immunohistochemistry (IHC)-based classification in 93% of the cases. For ten of the patients, being fusion gene positive, the fusion transcripts were detected in 100%. The molecular assessment of PD-L1 also showed agreement with the original assessment made by IHC. In conclusion, this study presents a small, targeted expression panel with the potential to perform both a molecularly based histological classification and a fusion gene identification in NSCLC patients as well as identifying PD-L1 status from a very limited amount of starting material. READ ARTICLE

Experimental and Molecular Pathology DOI:10.1016/j.yexmp.2022.104749

Authors: Anita Tranberg Simonsen, Amalie Utke, Johanne Lade-Keller, Lasse Westphal Thomsen, Torben Steiniche, Magnus Stougaard

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Case StudyKirk SmithRNA expression, NSCLC, NGS, Gene fusion, PD-L1
BRIEF REPORT: Plasma genotyping at the time of diagnostic tissue biopsy decreases time to treatment in patients with advanced NSCLC – results from a prospective pilot study
BRIEF REPORT: Plasma genotyping at the time of diagnostic tissue biopsy decreases time to treatment in patients with advanced NSCLC – results from a prospective pilot study

Introduction: The availability of targeted therapies has transformed the management of advanced NSCLC; however, the majority of patients do not undergo guideline-recommended tumor genotyping. The impact of plasma-based next-generation sequencing (NGS) performed simultaneously with diagnostic biopsy in suspected advanced NSCLC has largely been unexplored... Conclusions: Plasma-based NGS performed at the time of diagnostic biopsy in patients with suspected advanced NSCLC is associated with decreased time-to-treatment compared to usual care. READ ARTICLE

JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2022.100301

Authors: J. C. Thompson, C. Aggarwal, J. Wong, V. Nimgaonkar, W. Hwang, M. Andronov, D. M. Dibardino, C. T. Hutchinson, K. C. Ma, Lanfranco, E. Moon, A. R. Haas, A. P. Singh, C. A. Ciunci, M. Marmarelis, C. D’Avella, J. V. Cohen, J. M. Bauml, R. B. Cohen, C. J. Langer, A. Vachani, E. L. Carpenter

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Pre-ClinicalKirk SmithPlasma genotyping, tissue biopsy, NSCLC
Targeted RNA sequencing for upfront analysis of actionable driver alterations in non-small cell lung cancer
Targeted RNA sequencing for upfront analysis of actionable driver alterations in non-small cell lung cancer

OBJECTIVES: Targeted RNA-based Next-Generation Sequencing (tRNA-seq) is increasingly being used in molecular diagnostics for gene fusion detection in non-small cell lung cancer (NSCLC). However, few data support its clinical application for the detection of single nucleotide variants (SNVs) and small insertions/deletions. In this study, we evaluated the performance of tRNA-seq using Archer FusionPlex for simultaneous detection of actionable gene fusions, splice variants, SNVs and indels in formalin-fixed, paraffin-embedded NSCLC tissue... Conclusion: Our results demonstrate that tRNA-seq can be implemented in a diagnostic setting as an efficient strategy for simultaneous detection of actionable gene fusions, splice variants, SNVs and indels in NSCLC provided that adequate RNA-seq analysis tools are available, especially for the detection of indels. This approach allows upfront identification of currently recommended targetable molecular alterations in NSCLC samples. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2022.02.013

Authors: Sofie, Claerhout, Stefan Lehnert, Sara Vander Borght, Lien Spans, Christophe Dooms, Els Wauters, Johan Vansteenkiste, Birgit Weynand, Karen Deraedt, Claire Bourgain, Isabelle Vanden Bempt

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Case StudyKirk SmithNSCLC, tRNA-seq, Archer FusionPlex, bio-informatics pipeline, comprehensive molecular testing
The role of next-generation sequencing in detecting gene FUSIONS with KNOWN and UNKNOWN partners: A single-center experience with methodologies’ integration
The role of next-generation sequencing in detecting gene FUSIONS with KNOWN and UNKNOWN partners: A single-center experience with methodologies’ integration

Aims: Next-generation sequencing (NGS) is becoming a new gold standard for determining molecular predictive biomarkers. This study aimed to evaluate the reliability of NGS in detecting gene fusions, focusing on comparing gene fusions with known and unknown partners... Conclusions: NGS is a reliable method for detecting gene fusions with known partners, but it is less accurate in identifying gene fusions with unknown partners, for which further analyses (such as FISH) are required. READ ARTICLE

Human Pathology DOI:10.1016/j.humpath.2022.02.005

Authors: Andrea Ambrosini-Spaltro, Anna Farnedi, Daniele Calistri, Claudia Rengucci, Giovanna Prisinzano, Elisa Chiadini, Laura Capelli, Davide Angeli, Chiara Bennati, Mirca Valli, Giovanni De Luca, Dora Caruso, Paola Ulivi, Giulio Rossi

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Review PaperKirk SmithNext-generation sequencing, FISH, IHC, gene fusion, partner, NSCLC
YES1 and MYC Amplifications as Synergistic Resistance Mechanisms to Different Generation ALK Tyrosine Kinase Inhibitors in Advanced NSCLC: Brief Report of Clinical and Preclinical Proofs
YES1 and MYC Amplifications as Synergistic Resistance Mechanisms to Different Generation ALK Tyrosine Kinase Inhibitors in Advanced NSCLC: Brief Report of Clinical and Preclinical Proofs

Introduction: ALK tyrosine kinase inhibitors (TKIs) are the standard treatment for advanced ALK-positive NSCLC. Nevertheless, drug resistance inevitably occurs. Here, we report a case of a patient with metastatic ALK-positive lung adenocarcinoma with an impressive resistance to sequential treatment with ALK TKIs mediated by YES1 and MYC amplification in a contest of epithelial-to-mesenchymal transition and high progressive chromosomal instability... Conclusions: In conclusion, YES1 and MYC amplifications are candidates to justify a rapid acquired resistance to crizotinib entailing primary brigatinib and lorlatinib resistance. In this context, a combination strategy of ALK TKI with dasatinib could be effective to overcome a rapid resistance. READ ARTICLE

JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2022.100278

Authors: Roberta Minari, Samuel Valentini, Denise Madeddu, Andrea Cavazzoni, Silvia La Monica, Costanza Anna Maria Lagrasta, Roberto Bertorelli, Veronica De Sanctis, Paola Fassan, Cinzia Azzoni, Lorena Bottarelli, Caterina Frati, Letizia Gnetti, Francesco Facchinetti, Pier Giorgio Petronini, Roberta Alfieri, Alessandro Romanel, Marcello Tiseo

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Case StudyKirk SmithNSCLC, ALK TKIs, Resistance mechanism, YES1 amplification, MYC amplification
Continuation of Lorlatinib in ALK-positive NSCLC Beyond Progressive Disease
Continuation of Lorlatinib in ALK-positive NSCLC Beyond Progressive Disease

Continuing LBPD is a viable treatment option for select patients with ALK-positive NSCLC who progressed on lorlatinib. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.12.011

Authors: Sai-Hong I.Ou, Benjamin J.Solomon, Alice T.Shaw, Shirish M.Gadgeel, BenjaminBesse, Ross A.Soo, Antonello Abbattista, Francesca Toffalorio, Robin Wiltshire, Alessandra Bearz

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Clinical TrialsKirk Smithlorlatinib, NSCLC, post-progression treatment, RECIST 1.1
Clinical Outcomes for Plasma-Based Comprehensive Genomic Profiling Versus Standard-of-Care Tissue Testing in Advanced Non–Small Cell Lung Cancer
Clinical Outcomes for Plasma-Based Comprehensive Genomic Profiling Versus Standard-of-Care Tissue Testing in Advanced Non–Small Cell Lung Cancer

Background: Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced nonsquamous non–small cell lung cancer (aNSCLC). The NILE study was a prospective observational study that demonstrated noninferiority of cell-free circulating tumor DNA (cfDNA)-based tumor genotyping compared to tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed nonsquamous aNSCLC. As the cohort has matured, clinical outcomes data can now be analyzed... Conclusions: cfDNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published targeted therapy outcomes with tissue profiling, even in community-based centers. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2021.10.001

Authors: Ray D. Page, Leylah M. Drusbosky, Hiba Dada, Victoria M. Raymond, Davey B. Daniel, Stephen G. Divers, Karen L. Reckamp, Miguel A. Villalona-Calero, Daniel Dix, Justin I. Odegaard, Richard B. Lanman, Vassiliki, A. Papadimitrakopoulou, Natasha B. Leighl

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Review PaperKirk SmithNSCLC, Targeted therapy, Genotyping, Liquid biopsy (cfDNA), Next-generation sequencing
Genetic landscape of patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study
Genetic landscape of patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study

NGS data were generated for 85 pts (ALKi-pretreated [n = 54]; ALKi-naïve [n = 31]), 57 were collected from patients before exposure to any ALKi. NGS did not detect ALK rearrangement in 14 of 85 patients; several of these ALK NGS negative cases harbored alternative drivers, e.g. EGFR mutation. Of the 71 biopsies with NGS confirmed ALK rearrangement, the most frequently detected rearrangements were EML4-ALK variant 1 (V1) and EML4-ALK V3 (36.6% [26/71] and 32.4% [23/71] respectively). Eight (six crizotinib-pretreated and two pretreated with crizotinib followed by alectinib) of the 21 ALKi-pretreated patients carried a point mutation of the ALK TKD, and had the biopsy collected between 1 and 14 days before ceritinib; with the exception of one patient with a G1202R point mutation, all patients derived clinical benefit from ceritinib treatment.
Of the 14 ALKi-naïve patients, ceritinib was effective in almost all patients, including a patient carrying a concomitant ERBB4 and HGF amplificatio..... READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.11.007

Authors: D.S-W.Tana, M.Thomas, DW.Kim, S. Szpakowski, P. Urban, R. Mehra, L.Q.M. Chow, S. Sharma, B.J. Solomon, E.Felip, D.R. Camidge, J. Vansteenkiste, L. Petruzzelli, S. Pantano and A.T. Shaw

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Clinical Trials, group1Kirk SmithCeritinib, NSCLC, Anaplastic lymphoma kinase (ALK), Gene expression profiling, Molecular cytogenetics
Analysis of methods in the Prospective Central Lung Cancer Biomarker Registry (LungPath) from the Spanish Society of Pathology (SEAP)
Analysis of methods in the Prospective Central Lung Cancer Biomarker Registry (LungPath) from the Spanish Society of Pathology (SEAP)

Aims The aim of this study is to extend the analysis of the Lung Cancer Biomarker Testing Registry (LungPath), by analysing the techniques used in the determination of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) for the diagnostic of patients with advanced non-small-cell lung cancer (NSCLC). Methods Information of the technique used for the determination of EGFR, ALK, ROS1 and PD-L1 was recorded from March 2018 to January 2019 from 44 centres, but only 34 centres matched with the 38 centres previously analysed, allowing to analyse the techniques used in 8970 matched determinations of EGFR, ALK, ROS1 and PD-L1. Therefore, a by-centre analysis studied the level of implementation of the techniques in the 44 centres, while a by-determination analysis made it possible to assess the overall frequency of the techniques used on the 9134 matched samples. Results By-centre analysis showed that only 46.5%..... READ ARTICLE

Journal of Clinical Pathology DOI:10.1136/jclinpath-2021-208034

Authors: Martín-López J, Rojo F, Martínez-Pozo A,Hernández-Iglesias T, Carcedo D, Ruiz de Alda L, García JF, Salas C

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Real-World Outcomes, group1Kirk SmithNSCLC, ALK, EGFR, ROS, Biomarker Testing
Outcomes of Gamma Knife Radiosurgery for Brain Metastases From Anaplastic Lymphoma Kinase Rearrangement-Positive and EGFR Mutation-Positive Non-Small Cell Lung Cancer
Outcomes of Gamma Knife Radiosurgery for Brain Metastases From Anaplastic Lymphoma Kinase Rearrangement-Positive and EGFR Mutation-Positive Non-Small Cell Lung Cancer

The outcomes after gamma knife radiosurgery (GKRS) were retrospectively analysed in patients with brain metastases from anaplastic lymphoma kinase (ALK) rearrangement-positive and epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) to evaluate the efficacy, safety and difference for overall survival and local tumor control. ALK rearrangement-positive NSCLC patients tended to have significantly longer survival, but had higher incidence of new intracranial metastases due to long-term survival after GKRS, compared with EGFR mutation-negative and driver gene mutation-negative NSCLC patients. GKRS induced significantly satisfactory local tumor control in driver gene mutation-positive tumors but GKRS-related complication frequency was higher, especially in ALK-positive NSCLC patients. Therefore, more careful imaging follow-up is necessary after GKRS for patients with driver gene mutation-positive NSCLC. READ ARTICLE

Cureus DOI:10.7759/cureus.20398

Authors: Matsunaga S and Shuto T

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Real-World Outcomes, group1Kirk SmithGamma Knife Radiosurgery (GKRS), Brain Metastases, ALK, EGFR, NSCLC
Management of Oligoprogression in Patients with Metastatic NSCLC Harboring ALK Rearrangements
Management of Oligoprogression in Patients with Metastatic NSCLC Harboring ALK Rearrangements

Personalized treatment based on driver molecular alterations, such as ALK rearrangement, has revolutionized the therapeutic management of advanced oncogene addicted NSCLC patients. Multiple effective ALK tyrosine kinase inhibitors (TKIs), with the amelioration of the activity at central nervous system level, are now available, leading to substantial prognosis improvement. The exposure to TKIs triggers resistance mechanisms and the sequential administration of other TKIs and chemotherapy is, for the most part, not targeted. In this context, extending the benefit deriving from precision medicine is paramount, above all when disease progression occurs in a limited number of sites. Retrospective data indicate that, in oligoprogressive disease, targeted therapy beyond progression combined with definitive local treatment of the progressing site(s) is an effective alternative. In these cases, multidisciplinary approach becomes essential for an integrated treatment strategy, depending on the s..... READ ARTICLE

Preprints DOI:10.20944/preprints202112.0145.v1

Authors: Pisano, C.; De Filippis, M.; Jacobs, F.; Novello, S.; Reale, M.L.

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Review Paper, Pre-PrintKirk Smitholigoprogression, NSCLC, ALK rearrangement
Pharmacovigilance Analysis of Cardiac Toxicities Associated With Targeted Therapies for Metastatic NSCLC
Pharmacovigilance Analysis of Cardiac Toxicities Associated With Targeted Therapies for Metastatic NSCLC

Targeted therapies have transformed treatment of driver-mutated metastatic NSCLC. We compared cardiovascular adverse events between and within targeted therapy classes. READ ARTICLE

Journal of Thoracic Oncology
DOI:10.1016/j.jtho.2021.07.030

Authors: Sarah Waliany, Han Zhu, Heather Wakelee, Sukhmani K. Padda, Millie Das, Kavitha Ramchandran, Nathaniel J. Myall, Thomas Chen, MD, Ronald M. Witteles, Joel W. Neal

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Review Paper, group1Kirk SmithNSCLC, Targeted therapies, Arrhythmia, Heart failure, Cardio-oncology
Blood First Assay Screening Trial (BFAST) in Treatment-Naive Advanced or Metastatic NSCLC: Initial Results of the Phase 2 ALK-Positive Cohort
Blood First Assay Screening Trial (BFAST) in Treatment-Naive Advanced or Metastatic NSCLC: Initial Results of the Phase 2 ALK-Positive Cohort

Introduction: The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort. Conclusions: These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.07.008

Authors: Rafal Dziadziuszko, Tony Mok, Solange Peters, Ji-Youn Han, Jorge Alatorre-Alexander,
Natasha Leighl, Virote Sriuranpong, Maurice Pérol, Gilberto de Castro Junior, Ernest Nadal, Filippo de Marinis, Osvaldo Arén Frontera, Daniel S.W. Tan, Dae Ho Lee, Hye Ryun Kim, Mark Yan, Todd Riehl, Erica Schleifman, Sarah M. Paul, Simonetta Mocci, Rajesh Patel, Zoe June Assaf, David S. Shames, Michael S. Mathisen, Shirish M. Gadgeel

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Clinical TrialsKirk SmithAlectinib, ALK-positive, Blood-based assay, Next-generation sequencing, NSCLC
Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials
Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials

Background
Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC.

Methods
We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases.


Results
A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg an..... READ ARTICLE

BMC Cancer DOI:10.1186/s12885-021-08977-0

Authors: Ma HC, Liu YH, Ding KL, Liu YF, Zhao WJ, Zhu YJ, Chang XS, Chen YD, Xiao ZZ, Yu YY, Zhou R, Zhang HB.

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Review Paper, group2Kirk SmithALK, NSCLC, First-line treatment, clinical trial meta-analysis
Genetic landscape of patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study
Genetic landscape of patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study

Objectives: To better understand genetic determinants of response to ceritinib, an exploratory analysis was conducted using tumor biopsies from anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients treated with ceritinib at doses of ≥ 300 mg in the ASCEND-1 study. Conclusions: This exploratory analysis highlights the potential role of NGS in improving our understanding of response and resistance to ceritinib. It also illustrates that ceritinib is active against almost all ALK resistance mutations found in ALKi-pretreated patients. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.11.007

Authors: D S-W Tan, M Thomas, D-W Kim, S Szpakowski, P Urban, R Mehra, L Q M Chow, S Sharma, B J Solomon, E Felip, D R Camidge, J Vansteenkiste, L Petruzzelli, S Pantano, A T Shaw

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Clinical TrialsKirk SmithALK, Anaplastic lymphoma kinase (ALK), Ceritinib, Gene expression profiling, Molecular cytogenetics, NSCLC, ASCEND-1
The impact of the ALK fusion variant on clinical outcomes in EML4-ALK patients with NSCLC: a systematic review and meta-analysis
The impact of the ALK fusion variant on clinical outcomes in EML4-ALK patients with NSCLC: a systematic review and meta-analysis

Background: Recent studies showed that ALK-fusion variants are associated with heterogeneous clinical outcomes. However, contradictory conclusions have been drawn in other studies showing no correlation between ALK variants and prognoses. Methods: A systematic review and meta-analysis was performed to evaluate the prognostic value of EML4-ALK fusion variants for patient outcomes. Results: 28 studies were included in the analysis. According to the pooled results, patients harboring variant 1 showed equivalent progression-free survival (PFS) and overall survival (OS) with non-v1 patients (hazard ratio [HR] for PFS: 0.91 [0.68–1.21]; p = 0.499; OS: 1.12 [0.73–1.72]; p = 0.610). Similarly, patients with v3 showed the same disease progress as non-v3 patients (pooled HR for PFS = 1.07 [0.72–1.58]; p = 0.741). However, pooled results for OS suggested that patients with v3 had worse survival than non-v3 patients (HR = 3.44 [1.42–8.35]; p = 0.006). Conclusion: Results suggest that patients with..... READ ARTICLE

Future Oncology DOI:10.2217/fon-2021-0945

Authors: Wang S, Luo R, Shi Y, Han X.

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Review Paper, group2Kirk SmithALK fusion, ALK rearrangement, ALK variant, NSCLC, prognosis
Discovery of 2,4-pyrimidinediamine derivatives as potent dual inhibitors of ALK and HDAC
Discovery of 2,4-pyrimidinediamine derivatives as potent dual inhibitors of ALK and HDAC

Combination of anaplastic lymphoma kinase (ALK) inhibitor with histone deacetylases (HDAC) inhibitor could exert synergistically anti-proliferative effects on ALK positive non-small cell lung cancer (NSCLC) naïve or resistant cells. In this work, we designed and synthesized a series of 2,4-pyrimidinediamine derivatives as dual ALK and HDAC inhibitors based on pharmacophore merged strategy. Among which, compound 10f displayed the most potent and balanced inhibitory activity against ALK (IC50 = 2.1 nM) and HDAC1 (IC50 = 7.9 nM), respectively. In particular, 10f was also potent against the frequently observed Crizotinib-resistant ALKL1196M (IC50 = 1.7 nM) as well as the Ceritinib-resistant ALKG1202R (IC50 = 0.4 nM) mutants. In antiproliferative activity assay, 10f exhibited impressive activity on ALK-addicted cancer cell lines at low micromole concentrations, which was comparable to that of Crizotinib and Ceritinib. Further flow cytometric analysis indicated that 10f could effectively ind..... READ ARTICLE

European Journal of Medicinal Chemistry DOI:10.1016/j.ejmech.2021.113672

Authors: Tao Pan, Yanrong Dan, Dafeng Guo, Junhao Jiang, Dongzhi Ran, Lin Zhang, Binghua Tian, Jianyong Yuan, Yu Yu, Zongjie Gan

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Pre-Clinical, group2Kirk SmithALK/HDAC dual Inhibitors, Pharmacophore merged strategy, NSCLC
Anaplastic lymphoma kinase rearrangement prevalence in patients with advanced non-small cell lung cancer in the United States: retrospective real world data
Anaplastic lymphoma kinase rearrangement prevalence in patients with advanced non-small cell lung cancer in the United States: retrospective real world data

This study assessed the prevalence of anaplastic lymphoma kinase (ALK) rearrangements in US oncology practices. The cohort included 19,895 eligible patients with a mean age 68.5 years, majority ever-smokers (85.5%) and from community centers (92.2%). The overall ALK rearrangement prevalence was 2.6%. Positivity rate varied by histology and smoking status; it was the highest among non-smoking patients with non-squamous histology (9.3%). Differences in ALK status also varied by age and race, with young patients (18–39 years) having a higher prevalence (21.6%) vs. older patients (age ≥55 = 2.2%); Asian patients had a prevalence of 6.3%. Patients that were positive for other mutations or rearrangements had a lower ALK positivity rate (0.5%) and patients positive for PD-L1 had a rate of 3.0%. Conclusion: The likelihood of finding an ALK translocation was highest in younger patients and nonsmokers; however, age and smoking history were not discriminative enough to exclude testing based on cl..... READ ARTICLE

Oncotarget DOI:10.18632/oncotarget.28114

Authors: Allen T. Craig, Xiao Y., Yang B., Croix D., Abraham A., Redpath S., Engstrom-Melynk J., Shah R., Madala J., Bernicker E. H.

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Real-World OutcomesKirk Smithlorlatinib, NSCLC, post-progression treatment, RECIST 1.1
F-circEA1 regulates cell proliferation and apoptosis through ALK downstream signaling pathway in non-small cell lung cancer
F-circEA1 regulates cell proliferation and apoptosis through ALK downstream signaling pathway in non-small cell lung cancer

Studies have confirmed that circular RNA (circRNA) has a stable closed
structure, which plays an important role in the progression of tumors.
Cancers with positive fusion genes can produce associated fusion circRNA
(F-cirRNA). However, there are no reports concerning a role for
F-circRNA of the echinoderm microtubule associated-protein like
4-anaplastic lymphoma kinase variant 1 (EML4-ALK1) in non-small cell
lung cancer (NSCLC). Our study confirmed the existence of fusion circEA1
(F-circEA1) in NCI-H3122 cells (carrying the EML4-ALK1 gene), F-circEA1
was expressed both in the cytoplasm and nucleus as determined by
fluorescence in situ hybridization (FISH) and Sanger sequencing. CCK8
and transwell assays showed that F-circEA1 was beneficial to cell
proliferation, metastasis, and invasion. Overexpression of F-circEA1 can
also promote cell proliferation, migration and invasion in A549 and
SPCA1 cells (non-small cell lung cancer cell line not carrying the
EML4-ALK1 gene). Int..... READ ARTICLE

Human Cell DOI:10.1007/s13577-021-00628-7

Authors: Yinping Huo, Tangfeng Lv, Mingxiang Ye, Suhua Zhu, Jiaxin Liu, Hongbing Liu & Yong Song

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Pre-Clinical, group2Kirk SmithF-circEA1, EML4-ALK, NSCLC, Apoptosis
Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis
Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis

Anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK-positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients. We find that neutropenia under crizotinib treatment was found to be associated with improved PFS suggesting that neutropenia might be an important determinant in treatment and survival strategies. READ ARTICLE

Indian Journal of Cancer DOI:10.4103/ijc.IJC_71_20

Authors: Pınar Gürsoy, Burcu Çakar, Deniz Nart, Erdem Göker

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Real-World OutcomesKirk SmithALK, NSCLC, crizotinib, AE, neutropenia, PFS