Posts tagged ROS1
Association of anticoagulant use with clinical outcomes from crizotinib in ALK- and ROS1-rearranged advanced non-small cell lung cancers: A retrospective analysis of PROFILE 1001
Association of anticoagulant use with clinical outcomes from crizotinib in ALK- and ROS1-rearranged advanced non-small cell lung cancers: A retrospective analysis of PROFILE 1001

Background: ROS1- and ALK-rearranged advanced NSCLCs are associated with increased thromboembolic risk. We hypothesized that a prothrombotic phenotype offers an evolutionary advantage to subsets of these cancers. The impact of this phenotype could alter outcomes from targeted therapy.

Methods: In a retrospective analysis of ROS1- and ALK-rearranged NSCLCs treated with crizotinib in a phase 1 trial, we compared progression-free survival (PFS) and objective response rate (ORR) based on the history of anticoagulation use (a possible surrogate of thromboembolism) at baseline (within 90 days before study enrollment) or within 90 days of study treatment.

Results: Twelve out of 53 (22.6%) ROS1- and 39 out of 153 (25.5%) ALK-rearranged NSCLCs received anticoagulation before or during the trial. Most ROS1 and ALK patients on anticoagulation received low-molecular-weight heparin (75% and 64.1%, respectively). In the ROS1-rearranged group, the median PFS (95% CI) values were 5.1 (4.4-14.4) and 29.0 (16.5-48.8) months, and the ORR values were 41.7% (95% CI: 15.2 to 72.3) and 80.5% (95% CI: 65.1 to 91.2) among those with and without anticoagulation treatment, respectively. In the ALK-rearranged group, the median PFS (95% CI) was 7.1 (5.4-7.7) and 12.0 (9.4-18.3) months, and the ORR was 41% (95% CI: 25.6 to 57.9) and 74.3% (95% CI: 65.3 to 82.1) among those with and without anticoagulation, respectively.

Conclusions: Anticoagulation (as a potential surrogate of a prothrombotic subset) in ROS1- and ALK-rearranged NSCLCs may be associated with a lower PFS and ORR to crizotinib. READ ARTICLE

Cancer Medicine DOI:10.1002/cam4.4789.

Authors: Ng TL, Tsui DCC, Wang S, Usari T, Patil T, Wilner K, Camidge DR.

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Clinical TrialsKirk SmithALK, ROS1, crizotinib, lung cancer, thromboembolism
Safety and activity of WX-0593 (Iruplinalkib) in patients with ALK- or ROS1-rearranged advanced non-small cell lung cancer: a phase 1 dose-escalation and dose-expansion trial
Safety and activity of WX-0593 (Iruplinalkib) in patients with ALK- or ROS1-rearranged advanced non-small cell lung cancer: a phase 1 dose-escalation and dose-expansion trial

WX-0593 (Iruplinalkib) is a novel, highly selective oral ALK and ROS1 tyrosine kinase inhibitor (TKI). In this study, the safety, antitumor activity, and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer (NSCLC) patients with ALK or ROS1 rearrangement. In the dose-escalation phase and dose-expansion phase, patients were treated with WX-0593 until disease progression, unacceptable toxicity, or subject withdrawal. In the dose-escalation phase, the primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety assessed by investigators. In the dose-expansion phase, the primary endpoint was objective response rate (ORR) assessed by investigators. Between September 25, 2017 and October 15, 2018, a total of 153 patients received WX-0593 treatment. Two dose-limiting toxicities (DLTs) including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient. MTD was not rea..... READ ARTICLE

Signal Transduction and Targeted Therapy DOI:10.1038/s41392-021-00841-8

Authors: Shi, Y., Fang, J., Hao, X. et al.

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Clinical TrialsKirk SmithWX-0593 (Iruplinalkib), ALK, ROS1, tyrosine kinase inhibitor (TKI), maximum tolerated dose (MTD), dose-limiting toxicity (DLT)
Multiplex fluorescence in situ hybridization testing for anaplastic lymphoma kinase and c-ros oncogene 1 gene rearrangements on cytology smears in lung adenocarcinomas:..
Multiplex fluorescence in situ hybridization testing for anaplastic lymphoma kinase and c-ros oncogene 1 gene rearrangements on cytology smears in lung adenocarcinomas:..

Introduction: Multiplex anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) fluorescence in situ hybridization (FISH) probes conserve tissue by analyzing both ALK and ROS1 gene rearrangements (ALK-R/ROS1-R) in a single test. The positivity cutoffs have been validated on formalin-fixed, paraffin-embedded (FFPE) tissue sections and not tested on non–cell block (CB) cytology preparations. We sought to validate non-CB cytology preparations for the detection of ALK-R/ROS1-R using multiplex ALK/ROS1 FISH probes by comparing the results with matched FFPE results... Conclusions: Non-CB cytology smears are highly suitable for multiplex FISH analysis with 100% concordance with FFPE FISH and/or ALK D5F3 companion diagnostics assay results. READ ARTICLE

Journal of the American Society of Cytopathology DOI:10.1016/j.jasc.2022.01.001

Authors: Aruna Nambirajan, Deeksha Rana, Komal Samant, Aswini Prabakaran, Prabhat Malik, Deepali Jain

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Review PaperKirk SmithALK, ROS1, Multiplex FISH, Cytology smear, Lung adenocarcinoma
SHP2 inhibition enhances the effects of tyrosine kinase inhibitors in preclinical models of treatment-naïve ALK-, ROS1-, or EGFR-altered non-small-cell lung cancer
SHP2 inhibition enhances the effects of tyrosine kinase inhibitors in preclinical models of treatment-naïve ALK-, ROS1-, or EGFR-altered non-small-cell lung cancer

After molecular-targeted therapy, some cancer cells may remain that are resistant to therapies targeting oncogene alterations, such as those in the genes encoding the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) as well as c-ros oncogene 1 (ROS1). The mechanisms underlying this type of resistance are unknown. Here we report the potential role of Src homology 2 domain-containing phosphatase 2 (SHP2) in the residual cells of ALK/ROS1/EGFR-altered non-small-cell lung cancer (NSCLC). Molecular-targeted therapies failed to inhibit the ERK signaling pathway in the residual cells whereas the SHP2 inhibitor SHP099 abolished their remaining ERK activity. SHP099 administered in combination with molecular-targeted therapy resulted in marked growth inhibition of cancer cells both in vitro and in vivo. Thus, treatment combining an SHP2 inhibitor and a tyrosine kinase inhibitor may be a promising therapeutic strategy for oncogene-driven NSCLC. READ ARTICLE

Molecular Cancer Therapeutics DOI: 10.1158/1535-7163.MCT-20-0965

Authors: Hirohisa Kano, Eiki Ichihara, Hiromi Watanabe, Kazuya Nishii, Chihiro Ando, Takamasa Nakasuka, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda and Katsuyuki Kiura

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Pre-Clinical, group5Kirk SmithALK, ROS1, EGFR, SHP2, NSCLC, ERK
Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion–Positive Lung Cancer
Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion–Positive Lung Cancer

We performed molecular profiling of the largest series to date of crizotinib- and lorlatinib-resistant biopsies, finding that ROS1 kinase domain mutations mediate resistance in one third to one half of cases, respectively. Recurrent resistance mutations in ROS1 included G2032R and less well-characterized L2086F. In Ba/F3 models, type I inhibitors, including crizotinib, entrectinib, and lorlatinib, were unable to overcome ROS1L2086F, whereas type II inhibitor, cabozantinib, maintained potency. We additionally detected MET and RAS-MAPK alterations in resistant specimens. Our study highlights the importance of developing novel ROS1 inhibitors with potency against recurrent ROS1 resistance mutations and may inform sequential treatment strategies in ROS1+ lung cancer. ROS1 mutations mediate resistance to crizotinib and lorlatinib in more than one third of cases, underscoring the importance of developing next-generation ROS1 inhibitors with potency against these mutations, including G2032R and L2086F. Continued efforts are needed to elucidate ROS1-independent resistance mechanisms. READ ARTICLE

Cancer Mechanisms and Therapy DOI:10.1158/1078-0432.CCR-21-0032

Authors: Jessica J. Lin, Noura J. Choudhury, Satoshi Yoda, Viola W. Zhu, Ted W. Johnson, Ramin Sakhtemani, Ibiayi Dagogo-Jack, Subba R. Digumarthy, Charlotte Lee, Andrew Do, Jennifer Peterson, Kylie Prutisto-Chang, Wafa Malik, Harper G. Hubbeling, Adam Langenbucher, Adam J. Schoenfeld, Christina J. Falcon, Jennifer S. Temel, Lecia V. Sequist, Beow Y. Yeap, Jochen K. Lennerz, Alice T. Shaw, Michael S. Lawrence, Sai-Hong Ignatius Ou, Aaron N. Hata, Alexander Drilon, Justin F. Gainor

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Real-World OutcomesKirk Smithcrizotinib, lorlatinib, ROS1
Clinical Relevance of an Amplicon-Based Liquid Biopsy for Detecting ALK and ROS1 Fusion and Resistance Mutations in Patients With Non–Small-Cell Lung Cancer
Clinical Relevance of an Amplicon-Based Liquid Biopsy for Detecting ALK and ROS1 Fusion and Resistance Mutations in Patients With Non–Small-Cell Lung Cancer

PURPOSE Liquid biopsy specimen genomic profiling is integrated in non–small-cell lung cancer (NSCLC) guidelines; however, data on the clinical relevance for ALK/ROS1 alterations are scarce. We evaluated the clinical utility of a targeted amplicon-based assay in a large prospective cohort of patients with ALK/ROS1-positive NSCLC and its impact on outcomes. CONCLUSION Next-generation, targeted, amplicon-based sequencing for liquid biopsy specimen profiling provides clinically relevant detection of ALK/ROS1 fusions in TKI-naïve patients and allows for the identification of resistance mutations in patients treated with TKIs. Liquid biopsy specimens from patients treated with TKIs may affect clinical outcomes and capture heterogeneity of TKI resistance, supporting their role in selecting sequential therapy. READ ARTICLE

JCO Precision Oncology DOI:10.1200/PO.19.00281

Authors: Laura Mezquita, Aurélie Swalduz, Cécile Jovelet, Sandra Ortiz-Cuaran, Karen Howarth, David Planchard, Virginie Avrillon, Gonzalo Recondo, Solène Marteau, Jose Carlos Benitez, Frank De Kievit, Vincent Plagnol, Ludovic Lacroix, Luc Odier, Etienne Rouleau, Pierre Fournel, Caroline Caramella, Claire Tissot, Julien Adam, Samuel Woodhouse, Claudio Nicotra, Edouard Auclin, Jordi Remon, Clive Morris, Emma Green, Christophe Massard, Maurice Pérol, Luc Friboulet, Benjamin Besse, and Pierre Saintigny

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Real-World OutcomesKirk SmithNext-generation sequencing, liquid biopsy, ALK, ROS1, resistance
Molecular diagnosis in non-small-cell lung cancer: expert opinion on ALK and ROS1 testing
Molecular diagnosis in non-small-cell lung cancer: expert opinion on ALK and ROS1 testing

The effectiveness of targeted therapies with tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) depends on the accurate determination of the genomic status of the tumour. For this reason, molecular analyses to detect genetic rearrangements in some genes (ie, ALK, ROS1, RET and NTRK) have become standard in patients with advanced disease. Since immunohistochemistry is easier to implement and interpret, it is normally used as the screening procedure, while fluorescence in situ hybridisation (FISH) is used to confirm the rearrangement and decide on ambiguous immunostainings. Although FISH is considered the most sensitive method for the detection of ALK and ROS1 rearrangements, the interpretation of results requires detailed guidelines. In this review, we discuss the various technologies available to evaluate ALK and ROS1 genomic rearrangements using these techniques. Other techniques such as real-time PCR and next-generation sequencing have been developed recently to evaluat..... READ ARTICLE

Journal of Clinical Pathology DOI:10.1136/jclinpath-2021-207490

Authors: Esther Conde, Federico Rojo, Javier Gómez, Ana Belén Enguita, Ihab Abdulkader, Ana González, Dolores Lozano, Nuria Mancheño, Clara Salas, Marta Salido, Eduardo Salido-Ruiz, Enrique de Álava

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Review PaperKirk SmithALK, ROS1, molecular diagnosis
Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program
Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program

Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis. READ ARTICLE

Therapeutic advances in Medical Oncology DOI: 10.1177/1758835920980558

Authors: Nikolaj Frost, Petros Christopoulos, Diego Kauffmann-Guerrero, Jan Stratmann, Richard Riedel, Monica Schaefer, Jürgen Alt, Sylvia Gütz, Daniel C Christoph, Eckart Laack, Martin Faehling, Richard Fischer, Klaus Fenchel, Sebastian Haen, Lukas Heukamp, Christian Schulz and Frank Griesinger

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Real-World OutcomesKirk SmithALK, non-small cell lunb cancer (NSCLC), ROS1, TP53, brain metastases, early access program, lorlatinib
Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program
Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program

We report on the results of the German early access program (EAP) with the
third-generation ALK- and ROS1-inhibitor lorlatinib. Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis. READ ARTICLE

Therapeutic advances in Medical Oncology DOI: 10.1177/1758835920980558

Authors: Nikolaj Frost, Petros Christopoulos, Diego Kauffmann-Guerrero, Jan Stratmann, Richard Riedel, Monica Schaefer, Jürgen Alt, Sylvia Gütz, Daniel C. Christoph, Eckart Laack, Martin Faehling, Richard Fischer, Klaus Fenchel, Sebastian Haen, Lukas Heukamp, Christian Schulz, Frank Griesinger

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Real-World OutcomesKirk SmithALK, brain metastases, early access program, NSCLC, ROS1, TP53, lorlatinib
Overcoming TKI resistance in fusion-driven NSCLC: new generation inhibitors and rationale for combination strategies
Overcoming TKI resistance in fusion-driven NSCLC: new generation inhibitors and rationale for combination strategies

Targeted therapies lead to acquired resistance through multiple mechanisms. The selective pressure of newer, more potent TKIs results in new resistance mechanisms. Article gives overview of strategies for overcoming resistance to TKIs targeting the common oncogenic gene fusions in NSCLC. READ ARTICLE

Translational Lung Cancer Research DOI: 10.21037/tlcr-2019-cnsclc-06

Authors: Alessandro Russo, Andrés F. Cardona, Christian Caglevic, Paolo Manca, Alejandro Ruiz-Patiño, Oscar Arrieta, Christian Rolfo

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Review PaperKirk SmithALK, RET, acquired resistance, ROS1, NTRK
Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy
Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy

Personalized medicine holds promise to tailor the treatment options for patients’ unique genetic make-up, behavioral and environmental background. Liquid biopsy is non-invasive technique and precise diagnosis and treatment approach. Significantly, NGS technologies have revolutionized the genomic medicine by novel identifying SNPs, indel mutations in both coding and non-coding regions and also a promising technology to accelerate the early detection and finding new biomarkers for diagnosis and treatment. The number of the bioinformatics tools have been rapidly increasing with the aim of learning more about the detected mutations either they have a pathogenic role or not. EGFR, ROS1 and ALK genes are members of the RTK family. Until now, mutations within these genes have been associated with many cancers and involved in resistance formation to TKIs. This review article summarized the findings about the mostly investigated variations in EGFR, ROS1 and ALK genes and their potential role in..... READ ARTICLE

Critical Reviews in Oncology/Hematology DOI:10.1016/j.critrevonc.2020.103113

Authors: Mahmut Cerkez Ergoren, Havva Cobanogulları, Sehime Gulsun Temel, Gamze Mocan

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Review PaperKirk SmithEGFR, ROS1, ALK, Tyrosine kinase inhibitors, Liquid biopsy, Personalized therapy
Clinicopathological features and immunohistochemical utility of NTRK-, ALK-, and ROS1-rearranged papillary thyroid carcinomas and anaplastic thyroid carcinomas
Clinicopathological features and immunohistochemical utility of NTRK-, ALK-, and ROS1-rearranged papillary thyroid carcinomas and anaplastic thyroid carcinomas

NTRK1/3, ALK, and ROS1 translocations have been reported in a minor subset of papillary thyroid carcinomas (PTCs). We aimed to elucidate the prevalence and clinicopathological characteristics of these gene rearrangements and the utility of immunohistochemistry (IHC) in PTC and anaplastic thyroid carcinoma (ATC). We screened nonradiation-exposed cases of 307 PTCs and 16 ATCs by IHC for pan-Trk, ALK, and ROS1, followed by fluorescence in situ hybridization (FISH). In the PTC group, IHC for pan-Trk, ALK, and ROS1 was positive in 18 cases (5.9%), 1 case (0.3%), and 12 cases (3.9%), respectively. Among the pan-Trk IHC–positive cases (n = 18), 2 cases (11.1%; 0.7% of all PTCs) had NTRK1 or NTRK3 gene rearrangement with conventional PTC histology. The ALK IHC–positive case (n = 1) was the follicular variant of PTC with consistent ALK gene rearrangement. ROS1 gene rearrangement was not detectable in the ROS1 IHC–positive PTCs (0/12) by FISH. Most (approximately 70%) of the pan-Trk or ROS1 IHC–..... READ ARTICLE

Human Pathology DOI:10.1016/j.humpath.2020.09.004

Authors: Yui Nozaki, Hidetaka Yamamoto, Takeshi Iwasaki, Masanobu Sato, Rina Jiromaru, Takahiro Hongo, Ryuji Yasumatsu, Yoshinao Oda

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Case StudyKirk SmithPapillary thyroid carcinoma, Anaplastic thyroid carcinoma, pan-Trk, NTRK, ALK, ROS1
Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis
Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis

In clinical practice, patients with anaplastic lymphoma kinase (ALK)-rearrangement–positive non–small-cell lung cancer commonly receive sequential treatment with ALK tyrosine kinase inhibitors. The third-generation agent lorlatinib has been shown to inhibit a wide range of ALK resistance mutations and thus offers potential benefit in later lines, although real-world data are lacking. This multicenter study retrospectively investigated later-line, real-world use of lorlatinib in patients with advanced ALK- or ROS1-positive lung cancer. Fifty-one patients registered in a compassionate use program in Austria, who received second- or later-line lorlatinib between January 2016 and May 2020, were included in this retrospective real-world data analysis. Median follow-up was 25.3 months. Median time of lorlatinib treatment was 4.4 months for ALK-positive and 12.2 months for ROS-positive patients. ALK-positive patients showed a response rate of 43.2%, while 85.7% percent of the ROS1-positive pa.....READ ARTICLE

Pharmaceuticals DOI: 10.3390/ph13110371

Author: Maximilian J. Hochmair, Hannah Fabikan ,Oliver Illini, Christoph Weinlinger ,Ulrike Setinek, Dagmar Krenbek , Helmut Prosch , Markus Rauter ,Michael Schumacher ,Ewald Wöll ,Romana Wass ,Elmar Brehm ,Gudrun Absenger , Tatjana Bundalo , Peter Errhalt , Matthias Urban and Arschang Valipour

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Real-World OutcomesKirk SmithALK, ROS1, tyrosine kinase inhibitor, sequential treatment, lorlatinib
Fragment-based modification of 2,4-diarylaminopyrimidine derivatives as ALK and ROS1 dual inhibitors to overcome secondary mutants
Fragment-based modification of 2,4-diarylaminopyrimidine derivatives as ALK and ROS1 dual inhibitors to overcome secondary mutants

In order to explore novel ALK and ROS1 dual inhibitors capable of overcoming crizotinib-resistant mutants, two series of 2,4-diarylaminopyrimidine derivatives were designed, synthesized and evaluated for their in vitro cytotoxic activity. In this work, we retained the 2,4-diarylaminopyrimidine scaffold and derivatize the DAAP scaffold with sulfonyl and acrylamide moieties to extend the structure–activity relationship (SAR) study. To our delight, some compounds exhibited excellent inhibitory activity with a double-digit nanomolar level in MTT assay. Four compounds were selected for enzymic assays further, the results led to the identification of a potent ALK and ROS1 dual inhibitor X-17, with IC50 values of 3.7 nM, 2.3 nM, 8.9 nM and 1.9 nM against ALK, ALKL1196M, ALKG1202R and ROS1, respectively. Ultimately, the molecular docking studies on X-17 clearly disclosed reasonable and optimal binding interactions with ALK. READ ARTICLE

Bioorganic & Medicinal Chemistry DOI:10.1016/j.bmc.2020.115719

Authors: Minglin Zhu, Wei Li, Tianming Zhao, Yuxiang Chen, Tong Li, Shangfei Wei, Ming Guo, Xin Zhai

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Pre-ClinicalKirk Smith2, 4-Diarylaminopyrimidine, Dual inhibitor, ALK, ROS1, Crizotinib-resistant
GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients
GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib... Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ± 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ± 24 months is unprecedented for ROS1(+) NSCLC. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.07.022

Authors: Nir Peled, Roni Gillis, Saadettin Kilickap, Patrizia Froesch, Sergei Orlov, Elena Filippova, Umut Demirci, Petros Christopoulos, Irfan Cicin, Fatma Bugdayci Basal, Cengiz Yilmaz, Moiseenko Fedor, Taner Korkmaz, Semra Paydas, Oliver Gautschi, Alisan Zirtiloglu, Yesim Eralp, Havva Yesil Cinkir,… Laila C. Roisman

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Real-World OutcomesKirk SmithLorlatinib, Real-world data, ALK, ROS1
International Real-World Analysis of Efficacy and Safety of Lorlatinib Through Expanded Access Programs in Patients With Tyrosine Kinase Inhibitor–Refractory ALK-Positive or ROS1-Positive NSCLC
International Real-World Analysis of Efficacy and Safety of Lorlatinib Through Expanded Access Programs in Patients With Tyrosine Kinase Inhibitor–Refractory ALK-Positive or ROS1-Positive NSCLC

Lorlatinib exhibited meaningful activity in TKI-refractory ALK+ or ROS1+ patients with NSCLC enrolled in early or expanded access programs. READ ARTICLE

Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2020.04.019

Authors: Viola W. Zhu, Yen-Ting Lin, Dong-Wan Kim, Herbert H. Loong, Misako Nagasaka, Hao To, Yvonne Li-En Ang, Chan-Young Ock, Nishan Tchekmedyian, Sai-Hong Ignatius Ou, Nicholas L. Syn, Thanyanan Reungwetwattana, Chia-Chi Lin, Ross A. Soo

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Clinical TrialsKirk SmithLorlatinib Expanded access, TKI-refractory, ALK, ROS1, non-small cell lung cancer (NSCLC)
EGFR mutations and ROS1 and ALK rearrangements in a large series of non-small cell lung cancer in South India
EGFR mutations and ROS1 and ALK rearrangements in a large series of non-small cell lung cancer in South India

Aim of this study was to analyse the frequency of epidermal growth factor receptor (EGFR) mutations, ALK and ROS1 rearrangements and their association with age and gender in non-small cell lung cancer reported from a tertiary care center in South India. The study found EGFR mutations are more common than ALK and ROS1 rearrangements. They are more common in females. Patients less than 36 years have reduced frequency of EGFR mutations. Exon 19 deletion and L858R are most common and are more prevalent in lung adenocarcinomas. Rare EGFR mutations are seen in patients aged more than 50 years. READ ARTICLE

Cancer Reports DOI:10.1002/cnr2.1288

Authors: Anil Tarigopula, Gayathri Ramasubban, Vani Chandrashekar, Perumal Govindasami, hitra Chandran

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Real-World OutcomesKirk SmithALK, EGFR, non-small cell lung carcinoma, ROS1
Les réarrangements moléculaires : cibles thérapeutiques en cancérologie thoracique Fusion transcripts: Therapeutic targets in thoracic oncology
Les réarrangements moléculaires : cibles thérapeutiques en cancérologie thoracique Fusion transcripts: Therapeutic targets in thoracic oncology

Five to ten percent of lung adenocarcinoma harbor chromosomal rearrangements affecting the ALK, ROS1, NTRK and RET genes. These rearrangements are associated with the production of fusion transcripts that lead to the synthesis of chimeric proteins with constitutive kinase activity. These abnormal proteins induce an oncogenic dependency that may be targeted by tyrosine kinase inhibitors. In this review, we will summarize the clinical and molecular epidemiology of chromosomal rearrangements affecting ALK, ROS1, NTRK and RET genes. We will describe the mechanisms of resistance to tyrosine kinase inhibitors that have been reported. We will present the molecular techniques that can be used to detect these rearrangements and the strategies set-up by the molecular oncology laboratories to diagnose these genetic alterations. READ ARTICLE

Bulletin du Cancer DOI:10.1016/j.bulcan.2020.05.008

Authors: Audrey Mansuet-Lupo, Simon Garinet, Diane Damotte, Marco Alifano, Hélène Blons, Marie Wislez, Karen Leroy

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Review PaperKirk SmithRearrangement, Fusion, ALK, ROS1, RET, NTRK