ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice

Hofman, Paul

doi:10.3390/cancers9080107

Cited by 53 publications

(41 citation statements)

References 133 publications

(167 reference statements)

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“…ALK‐ rearrangements have been discovered recently as an important driver mutation in NSCLC, and especially in advanced‐stage NSCLC, ALK‐ mutation status has a major impact on how patients are treated . ALK rearrangement is found in 3%–7% of patients suffering from stage IIIB or stage IV NSCLC, according to previous data . Adenocarcinomas harbor ALK mutations more frequently than squamous cell carcinomas.…”

Section: Introductionmentioning

confidence: 74%

Oncogene addiction and tumor mutational burden in non‐small‐cell lung cancer: Clinical significance and limitations

2019

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Lung cancer incidence has increased worldwide over the past decades, with nonsmall cell lung cancer (NSCLC) accounting for the vast majority (85%) of lung cancer specimens. It is estimated that lung cancer causes about 1.7 million global deaths per year worldwide. Multiple trials have been carried out, with the aim of finding new effective treatment options. Lately, special focus has been placed on immune checkpoint (PD1/PD-L1) inhibitors which impact the tumor immune microenvironment. Tumor mutational burden (TMB) has been found to predict response to immune checkpoint inhibitors. Conversely, recent studies have weakened the significance of TMB as a predictor of response to therapy and survival. In this review article, we discuss the significance of TMB, as well as possible limitations. Furthermore, we give a concise overview of mutations frequently found in NSCLC, and discuss the significance of oncogene addiction in lung cancer as an essential driver of tumorigenesis and tumor progression. Key points1. Tumor mutational burden (TMB) predicts response to immune checkpoint inhibitors 2. Recent studies have shown, however, that TMB has significant limitations 3. Oncogene addicted cancers are driven by one predominant driver mutation 4. Targeted agents are used as first-line treatment in certain types of NSCLC

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Section: Introductionmentioning

confidence: 74%

Oncogene addiction and tumor mutational burden in non‐small‐cell lung cancer: Clinical significance and limitations

2019

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“…As for EGFR the detection of an ALK rearrangement can be done with a LB, at the time of diagnosis of the disease, when a tissue biopsy cannot be performed or when the RNA from tissue sample is quantitatively or qualitatively inadequate [ 19 , 20 , 21 , 22 , 25 ]. Several targeted methods can be used, including RT-PCR with plasma RNA or a platelet extract, multiplex analysis of a limited number of genes looking for fusions in ALK as well as in ROS1 , RET and/or NTRK or analysis of an extensive panel of a large number of genes using next-generation sequencing (NGS) approaches [ 19 , 20 , 21 , 22 , 25 ]. Regardless of the approach used, the sensitivity of the tests is globally lower than for the reference tests performed with tissue to evaluate the ALK status (e.g., immunohistochemistry or Fluorescent in situ Hybridization (FISH) [ 19 ].…”

Section: Evaluation Of the Alk Status With A LImentioning

confidence: 99%

Liquid Biopsy and Therapeutic Targets: Present and Future Issues in Thoracic Oncology

Hofman

2017

Cancers

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The practice of liquid biopsy (LB) has revolutionized the care of patients with metastatic lung cancer. Many oncologists now use this approach in daily practice, applying precise procedures for the detection of activating or resistance mutations in EGFR. These tests are performed with plasma DNA and have been approved as companion diagnostic test for patients treated with tyrosine kinase inhibitors. ALK is another important target in lung cancer since it leads to treatment of patients who are positive for a rearrangement in ALK identified with tumor tissue. By analogy with EGFR, LB for detection of genomic alterations in ALK (rearrangements or mutations) has been rapidly adopted in the clinic. However, this promising approach has some limitations and has not yet been disseminated as much as the blood test targeting EGFR. In addition to these two therapeutic targets LB can be used for evaluation of the genomic status of other genes of interest of patients with lung cancer (ROS1, RET, NTRK MET, BRAF, HER2, etc.). LB can be performed to evaluate a specific target or for a more or less complex panel of genes. Considering the number of potential targets for clinical trials, techniques of next-generation sequencing of circulating DNA are on the rise. This review will provide an update on the contribution of LB to care of patients with metastatic lung cancer, including the present limits of this approach, and will consider certain perspectives.

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“…Furthermore, also molecular biology approaches have been developed to detect ALK -R, including the reverse transcriptase-PCR (RT-PCR) and the new generation sequencing (NGS). NGS could improve the sensibility and the sensitivity of detection; however, further validation studies with regard to the treatment response are now required to its clinical use 4…”

Section: Introductionmentioning

confidence: 99%

Multiplex fluorescence in situ hybridisation to detect anaplastic lymphoma kinase and ROS proto-oncogene 1 receptor tyrosine kinase rearrangements in lung cancer cytological samples

et al. 2019

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AimsSeveral predictive biomarkers of response to specific inhibitors have become mandatory for the therapeutic choice in non-small-cell lung cancer (NSCLC). In most lung cancer patients, the biological materials available to morphological and molecular diagnosis are exclusively cytological samples and minimum tumour wastage is necessary. Multiplex fluorescence in situ hybridisation (mFISH) to detect simultaneously ALK-rearrangement and ROS1-rearrangement on a single slide could be useful in clinical practice to save cytological samples for further molecular analysis. In this study, we aim to validate diagnostic performance of multiplex ALK/ROS1 fluorescence in situ hybridisation (FISH) approach in lung adenocarcinoma cytological series compared with classic single break apart probes.MethodsWe collected a series of 61 lung adenocarcinoma cytological specimens enriched in tumours harbouring ALK-rearrangement and ROS1-rearrangement. ALK and ROS1 status were previously assessed by classic FISH test using single break apart probes and immunohistochemistry. Study population was composed of 6 ALK-positive, 2 ROS1-positive and 53 ALK/ROS1-wild type. All specimens were analysed by multiplex FISH assay using FlexISH ALK/ROS1 DistinguISH Probe Zytovision.ResultsThe dual ALK/ROS1 FISH probe test results were fully concordant with the results of previous single ALK and ROS1 FISH tests on two different slides. 6 ALK-positive and 2 ROS1-positive were confirmed through multiplex FISH test, without false-positive and false-negative results. Multiplex ALK/ROS1 FISH test results agreed with immunohistochemistry assay staining results.ConclusionMultiplex ALK/ROS1 FISH probe test is a useful tool to detect simultaneously ALK-rearrangement and ROS1-rearrangement on a single slide in cytological specimens with a small amount of biomaterial.

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ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice

Cited by 53 publications

References 133 publications

Oncogene addiction and tumor mutational burden in non‐small‐cell lung cancer: Clinical significance and limitations

Oncogene addiction and tumor mutational burden in non‐small‐cell lung cancer: Clinical significance and limitations

Liquid Biopsy and Therapeutic Targets: Present and Future Issues in Thoracic Oncology

Multiplex fluorescence in situ hybridisation to detect anaplastic lymphoma kinase and ROS proto-oncogene 1 receptor tyrosine kinase rearrangements in lung cancer cytological samples

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