Fusion proteins in lung cancer: addressing diagnostic problems for deciding therapy.
Federica Zito MarinoGreta AlìFrancesco FacchinettiLuisella RighiGabriella FontaniniGiulio RossiRenato FrancoPublished in: Expert review of anticancer therapy (2021)
Introduction: Gene fusions are frequent chromosomal aberrations in solid tumors. In Lung cancer (LC) several druggable-fusions involving tyrosine kinase receptor genes have been described, including ALK, ROS1, RET and NTRK. In non-small cell lung cancer, testing for targetable fusions has become a part of routine clinical practice, greatly impacting therapeutic choice for patients with these aberrations. Although substantial technologies for gene fusion detection have been implemented over time including; cytogenetic, Fluorescence in situ hybridization (FISH), Immunohistochemistry (IHC), Retro-transcription Real-Time PCR (RT-qPCR), to Next Generation Sequencing (NGS), nCounter system (Nanostring technology), several critical issues remain. To date, only the companion diagnostic tests FISH and IHC for ALK-rearrangements and NGS for ROS1-rearrangments were approved. Other fusion approved tests are currently unavailable.Areas covered: In this review, we explore current diagnostic problems of gene fusion detection relative to the technologies available, in order to clarify future standardization of analyses which determine therapeutic choices.Expert opinion: The establishment of a gold standard, an effective diagnostic algorithm, and a standardized interpretation for the analysis of each druggable-fusions in lung cancer is essential for adequate therapeutic management.
Keyphrases
- copy number
- real time pcr
- clinical practice
- tyrosine kinase
- genome wide
- genome wide identification
- mental health
- dna damage
- dna methylation
- advanced non small cell lung cancer
- epidermal growth factor receptor
- machine learning
- transcription factor
- reactive oxygen species
- label free
- gene expression
- loop mediated isothermal amplification
- mesenchymal stem cells
- circulating tumor cells