Fusion Oncogenes in Lung Adenocarcinoma: Molecular Mechanisms, Diagnostic Complexities, and Innovations in Targeted Therapies

DOI

10.2991/978-94-6463-976-6_11How to use a DOI?

Keywords

Fusion oncogenes; Rare sarcomas; Chromosomal translocations; Transcriptional dysregulation; Targeted therapy; Epigenetic Remodelling; Precision oncology

Abstract

Rare sarcomas are a spectrum of mesenchymal cancers which are characterised by common driver mutations with most being the result of recurrent chromosomal translocations that create oncogenic fusion proteins. These fusions (e.g., EWS–FLI1, CIC–DUX4, SS18–SSX and others) are dominant molecular drivers that reprogram transcription, chromatin structure, and key signalling pathways within the cell. In contrast to cancers genotyped by complex mutational landscapes, fusion-driven sarcomas are often dependent on a single initiating event, thereby serving as exemplary models for precision oncology. This review compares and contrasts the current state of knowledge regarding the structure, mechanisms of action, and oncogenic impact of leading fusion proteins. We focus here on how these chimeric drivers converge on fundamental signaling pathways, such as PI3K/AKT/mTOR, RAS/MAPK, IGF-1R and Wnt/β-catenin to drive uncontrolled proliferation and senescence evasion of tumor cells and to aberrantly engage the tumor microenvironment. Emergence of molecular diagnostics, including RNA sequencing, FISH and liquid biopsy has enhanced tumor type classification and identification of minimal residual disease. We further consider new treatment approaches aimed at directly or synthetically targeting fusion oncogenes as well as their synthetic lethal vulnerabilities, epigenetic alterations, and fusion-generated neoantigens. Ongoing difficulties include mechanisms of resistance, tumor heterogeneity and limited clinical trial availability because of the rare nature of this disease. Further incorporation of molecular profiling, functional genomics and novel therapeutic agents holds promise as a means to improve the results for patients with these aggressive tumors.

Copyright

© 2025 The Author(s)

Open Access

Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

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TY  - CONF
AU  - Aman Tiple
AU  - Chaitali Dhande
AU  - Preenon Bagchi
PY  - 2025
DA  - 2025/12/29
TI  - Fusion Oncogenes in Lung Adenocarcinoma: Molecular Mechanisms, Diagnostic Complexities, and Innovations in Targeted Therapies
BT  - Proceedings of the International Conference on Intelligent Information Systems Design and Indian Knowledge System Applications (ICISDIKSA 2026)
PB  - Atlantis Press
SP  - 160
EP  - 172
SN  - 1951-6851
UR  - https://doi.org/10.2991/978-94-6463-976-6_11
DO  - 10.2991/978-94-6463-976-6_11
ID  - Tiple2025
ER  -