ALK and ROS1 Rearrangements, Coexistence and Treatment in Epidermal Growth Factor Receptor-wild Type Lung Adenocarcinoma: a Multicenter Study of 732 Cases
Overview
Affiliations
Background: Anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements represent two most frequent fusion targets in lung adenocarcinoma. Our study was intended to explore the clinicopathological characteristics, coexistence and treatment of ALK/ROS1-rearranged patients of lung adenocarcinoma without epidermal growth factor receptor (EGFR) mutation.
Methods: Patients with wild-type EGFR mutation were screened for ALK/ROS1 at four domestic hospitals. ALK/ROS1 rearrangements were detected by reverse transcription-polymerase chain reaction (RT-PCR). Progression-free survival (PFS) curve was plotted with the Kaplan-Meier method.
Results: Among 732 eligible cases, ALK and ROS1 rearrangements were detected in 89 (12.2%) and 32 (4.4%) patients respectively. One patient harbored coexisting ALK/ROS1 fusion. Both ALK and ROS1-positive phenotypes were predominantly detected in younger non-smokers. More ALK/ROS1-rearranged patients were correlated with the expressions of TTF1, napsin A and solid predominant adenocarcinoma subtype. Thirty-three ALK and six ROS1 rearrangement patients received crizotinib treatment at an advanced stage. The median PFS was 9.5 months for ALK-positive patients and it was not attained in ROS1-rearranged counterparts.
Conclusions: The frequency of ALK and ROS1 rearrangements is elevated in EGFR-wild-type patients and the phenomenon of coexisting ALK/ROS1 has remained extremely rare. The rearrangements of ALK/ROS1 are correlated with age, smoking status, expressions of TTF1 & napsin A and solid predominant adenocarcinoma subtype.
Current treatment and novel insights regarding ROS1-targeted therapy in malignant tumors.
Li S, Zhang H, Chen T, Zhang X, Shang G Cancer Med. 2024; 13(8):e7201.
PMID: 38629293 PMC: 11022151. DOI: 10.1002/cam4.7201.
Lung adenocarcinoma patients with -rearranged tumors by sex and smoking intensity.
Peng Y, Ernani V, Liu D, Guo Q, Hopps M, Cappelleri J Heliyon. 2024; 10(7):e28285.
PMID: 38560203 PMC: 10981064. DOI: 10.1016/j.heliyon.2024.e28285.
Nguyen Hoang T, Nguyen T, Tran N, Nguyen Hoang V, Thi Dao H, Tran V Front Mol Biosci. 2024; 11:1334808.
PMID: 38404964 PMC: 10886136. DOI: 10.3389/fmolb.2024.1334808.
Progress of non-small-cell lung cancer with rearrangement.
Yang X, Tang Z, Li J, Jiang J, Liu Y Front Mol Biosci. 2024; 10:1238093.
PMID: 38187090 PMC: 10766828. DOI: 10.3389/fmolb.2023.1238093.
Brisudova A, Bielnikova-Krystofova H, Motyka O, Fritzova D, Katuchova V, Ponikelska N Pol J Microbiol. 2023; 72(4):467-475.
PMID: 38103007 PMC: 10725158. DOI: 10.33073/pjm-2023-044.