Identification of a novel WNK1–ROS1 fusion in a lung adenocarcinoma sensitive to crizotinib

Liu, Yutao; Liu, Tianfeng; Li, Nan; Wang, Tao; Pu, Yue; Lin, Rui

doi:10.1016/j.lungcan.2018.12.011

Cited by 19 publications

(13 citation statements)

References 10 publications

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“…ROS1 protein shows substantial homology to ALK (both belong to insulin receptor superfamily), particularly within the ATP binding site (84% homology) and the kinase domains (64% homology) [5,12]. Genomic alteration of ROS1 is well known and normally leads to gene fusion with several fusion partners (Table 1) [2,5,11,[13][14][15][16][17][18][19][20][21][22][23]; the resulting fusion proteins are robust oncogenic drivers [24]. As a consequence, ROS1 kinase activity is constitutively activated, leading to increased cell proliferation, survival and migration due to the upregulation of JAK/STAT, PI3K/AKT and MAPK/ERK signalling pathways [11].…”

Section: Ros1 Discovery and Signalling Pathwaymentioning

confidence: 99%

Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies

D’Angelo

Sobhani

Chapman

et al. 2020

Cancers

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The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.

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Section: Ros1 Discovery and Signalling Pathwaymentioning

confidence: 99%

Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies

D’Angelo

Sobhani

Chapman

et al. 2020

Cancers

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“…169 The fusion of ROS1 to different partners, including CD74 (most common), solute carrier family 34 member 2 (SLC34A2), fused in glioblastoma (FIG), syndecan (SDC), ezrin (EZR), leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3), tropomyosin 3 (TPM3), lysine-deficient protein kinase 1 (WNK1), and zinc finger CCHC-type containing 8 (ZCCHC8), leads to constitutive signaling of the RTK and unregulated growth of the tumor cell. 169,[238][239][240][241][242] ROS1 fusions have also been identified in glioblastoma, melanoma, angiosarcoma, cholangiosarcoma, and gastric, colorectal, and ovarian carcinomas. [243][244][245][246][247][248] Population-level studies suggest an incidence of ROS1 fusions in approximately 1 to 2% of NSCLC cases.…”

Section: Ros1 Fusionsmentioning

confidence: 99%

Targeted Therapy for Non-Small Cell Lung Cancer

Noor

Cummings

Johnson

et al. 2020

Semin Respir Crit Care Med

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Lung cancer is a heterogeneous disease, and the availability of comprehensive genomic profiling has allowed for the characterization of its molecular subtypes. This has increased the ability to deliver “personalized medicines” by tailoring therapies to target driver mutations in a patient's cancer. The development of targeted therapies for non-small cell lung cancer (NSCLC) has helped define the era of precision medicine throughout oncology. This article aims to contextualize recent research and provide an updated summary of targeted therapies available for patients with NSCLC. With practitioners and clinical researchers in mind, we note standard of care therapies, important approvals, practice guidelines, and treatments in development. The first section discusses mutations in the epidermal growth factor receptor (EGFR) gene, and the second section examines rearrangements in the anaplastic lymphoma kinase (ALK) and ROS1 fusions. Finally, we explore the rarer molecular alterations in BRAF, RET, MET, HER2, and KRAS. Given the many available therapies, it is important to understand the molecular alterations in NSCLC, and how to target them.

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“…57 The test considered to be the gold standard for the determination of translocation of ROS1 is FISH. 58,59 IHC methods are currently used as screening tests but, in view of the high false positive rate, tumour samples considered positive in IHC should be tested according to the FISH method. 60 Finally, RT-PCR techniques have also been successfully studied.…”

Section: Transthoracic Core Needle Biopsy Versus Bronchoscopy and Tramentioning

confidence: 99%

From Traditional Histology to Next-Generation Pathology: A Review of The Workflow for the Characterisation and Molecular Profiling of Non-Small Cell Lung Cancer Samples

2020

EMJ Oncol

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The clinical management of non-small cell lung cancer has shown unprecedented progress into the era of target therapies and immuno-oncology. Despite significant recent achievements in the treatment of these patients, identification of all the clinically actionable alterations required for patient management remains challenging, particularly when dealing with cytological or small bioptic samples. Many investigations have assessed the role of diagnostic tools currently available, including immunohistochemistry and sequencing assays. It is extremely important to be aware of the minimum adequacy criteria for pathology laboratories to ensure correct management of the biological samples in non-small cell lung cancer, including cytological, cell blocks, and histological specimens. In this review, the authors provide a comprehensive overview of the gold standard requirements, processing parameters, and turnaround time for the final integrated report, and additionally outline the values and limitations of the different bioptic strategies.

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Identification of a novel WNK1–ROS1 fusion in a lung adenocarcinoma sensitive to crizotinib

Cited by 19 publications

References 10 publications

Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies

Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies

Targeted Therapy for Non-Small Cell Lung Cancer

From Traditional Histology to Next-Generation Pathology: A Review of The Workflow for the Characterisation and Molecular Profiling of Non-Small Cell Lung Cancer Samples

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