One-Step Polymerase Chain Reaction-Free Nanowire-Based Plasma Cell-Free DNA Assay to Detect EML4-ALK Fusion and to Monitor Resistance in Lung Cancer

Background: Next-generation sequencing has mostly been used for genotyping cell-free DNA (cfDNA) in plasma. However, this assay has several clinical limitations. We evaluated the clinical utility of a novel polymerase chain reaction–free nanowire (NW)-based plasma cfDNA assay for detecting ALK fusion and mutations. Conclusion: The newly developed simple NW-based cfDNA assay may be clinically applicable for rapid diagnosis of ALK fusion with its variant forms and early detection of resistance. READ ARTICLE

The Oncologist DOI:10.1002/onco.13902

Authors: Youngjoo Lee, Youngnam Cho, Eun Young Park, Seong-Yun Park, Kum Hui Hwang, Ji-Youn Han

Treatment with Next-Generation ALK Inhibitors Fuels Plasma ALK Mutation Diversity

Purpose: Acquired resistance to next-generation ALK tyrosine kinase inhibitors (TKIs) is often driven by secondary ALK mutations. Here, we investigated utility of plasma genotyping for identifying ALK resistance mutations at relapse on next-generation ALK TKIs.
Experimental design: We analyzed 106 plasma specimens from 84 patients with advanced ALK-positive lung cancer treated with second- and third-generation ALK TKIs using a commercially available next-generation sequencing (NGS) platform (Guardant360). Tumor biopsies from TKI-resistant lesions underwent targeted NGS to identify ALK mutations.
Results: By genotyping plasma, we detected an ALK mutation in 46 (66%) of 70 patients relapsing on a second-generation ALK TKI. When post-alectinib plasma and tumor specimens were compared, there was no difference in frequency of ALK mutations (67% vs. 63%), but plasma specimens were more likely to harbor ≥2 ALK mutations (24% vs. 2%, P = 0.004). Among 29 patients relapsing on lorlatinib, plasm..... READ ARTICLE

Clinical Cancer Research DOI:10.1158/1078-0432.CCR-19-1436

Authors: Dagogo-Jack I, Rooney M, Lin JJ, Nagy RJ, Yeap BY, Hubbeling H, Chin E, Ackil J, Farago AF, Hata AN, Lennerz JK, Gainor JF, Lanman RB, Shaw AT.

Real-World OutcomesKirk SmithNovember 15, 2019Next-Generation ALK Inhibitors, Plasma, Mutation Diversity

Feasibility of liquid biopsy using plasma and platelets for detection of anaplastic lymphoma kinase rearrangements in non-small cell lung cancer

Purpose: Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes. Conclusion: Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors. READ ARTICLE

Journal of Cancer Research and Clinical Oncology DOI:10.1007/s00432-019-02944-w

Authors: Cheol-Kyu Park, Ji-Eun Kim, Min-Seok Kim, Bo-Gun Kho, Ha-Young Park, Tae-Ok Kim, Hong-Joon Shin, Hyun-Joo Cho, Yoo-Duk Choi, In-Jae Oh, Young-Chul Kim

A two-circular RNA signature as a noninvasive diagnostic biomarker for lung adenocarcinoma

A circRNA signature was identified as a potential noninvasive biomarker for LUAD diagnosis. This study aimed to evaluate whether circulating circRNAs could be used as diagnostic biomarkers for lung adenocarcinoma (LUAD). READ ARTICLE

Journal of Translational Medicine
DOI:10.1186/s12967-019-1800-z

Authors: Xiao-Xia Liu, Yi-E Yang, Xiao Liu, Meng-Yu Zhang, Rui Li, Yun-Hong Yin, and Yi-Qing Qu

Pre-ClinicalKirk SmithFebruary 18, 2019LUAD, CircRNA, Plasma, Diagnosis, Biomarker, Hsa_circ_0005962, Hsa_circ_0086414