Liquid biopsy for the detection of resistance mutations to ROS1 and RET inhibitors in non-small lung cancers: A case series study

Yoshitaka Seki; Tatsuya Yoshida; Takashi Kohno; Ken Masuda; Yusuke Okuma; Yasushi Goto; Hidehito Horinouchi; Noboru Yamamoto; Kazuyoshi Kuwano; Yuichiro Ohe

doi:10.1016/j.resinv.2022.08.002

Liquid biopsy for the detection of resistance mutations to ROS1 and RET inhibitors in non-small lung cancers: A case series study

Respir Investig. 2022 Nov;60(6):852-856. doi: 10.1016/j.resinv.2022.08.002. Epub 2022 Sep 9.

Authors

Affiliations

¹ Division of Respirology, Department of Internal Medicine, The Jikei University Katsushika Medical Center; Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan. Electronic address: yseki-jikd@umin.ac.jp.
² Division of Thoracic Oncology, National Cancer, Center Hospital, Tokyo, Japan.
³ Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
⁴ Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Japan.

PMID: 36089506
DOI: 10.1016/j.resinv.2022.08.002

Abstract

Liquid biopsy can identify gene alterations that are associated with resistance to fusion gene-targeted treatments. In this study, we present three cases of advanced non-small cell lung cancer (NSCLC) harboring gene fusions; cell-free DNA (cfDNA) was used to assess the resistance mutations. A patient with MET amplification underwent RET-fusion NSCLC treatment with selpercatinib. A patient with ROS1 G2032R underwent ROS1-fusion NSCLC treatment with crizotinib. A patient who underwent ROS1-fusion NSCLC treatment with crizotinib harbored no somatic mutations. This case series shows that cfDNA analysis can identify potentially actionable genomic alterations, after disease progression, in targeted therapy for fusion genes. TRIAL REGISTRATION: The study was registered in the UMIN Clinical Trial Registry (UMIN 000017581).

Keywords: Acquired resistance; Liquid biopsy; Lung cancer; Next-generation sequencing; Tyrosine kinase inhibitor.

Publication types

Case Reports

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / pathology
Cell-Free Nucleic Acids*
Crizotinib / therapeutic use
Drug Resistance, Neoplasm / genetics
Humans
Liquid Biopsy
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / pathology
Mutation
Oncogene Proteins, Fusion / genetics
Oncogene Proteins, Fusion / therapeutic use
Protein Kinase Inhibitors / therapeutic use
Protein-Tyrosine Kinases / genetics
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-ret / genetics

Substances

Crizotinib
Protein-Tyrosine Kinases
Oncogene Proteins, Fusion
Proto-Oncogene Proteins
Cell-Free Nucleic Acids
Protein Kinase Inhibitors
RET protein, human
Proto-Oncogene Proteins c-ret
ROS1 protein, human