[Fusion transcripts: Therapeutic targets in thoracic oncology]

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Lung adenocarcinoma frequently harbors chromosomal rearrangements involving ALK, ROS1, NTRK, and RET genes.
• These rearrangements result in fusion transcripts producing constitutively active chimeric proteins, driving oncogenesis.
• This oncogenic dependency presents a therapeutic target for tyrosine kinase inhibitors (TKIs).

Purpose of the Study:

• To review the clinical and molecular epidemiology of ALK, ROS1, NTRK, and RET gene rearrangements.
• To describe emerging mechanisms of resistance to TKIs.
• To outline molecular techniques and diagnostic strategies for detecting these genetic alterations.

Main Methods:

• Literature review of clinical and molecular studies.
• Analysis of data on gene rearrangements, fusion proteins, and TKI resistance.
• Summary of diagnostic methodologies in molecular oncology.

Main Results:

• Prevalence data on ALK, ROS1, NTRK, and RET rearrangements in lung adenocarcinoma.
• Characterization of various TKI resistance mechanisms.
• Overview of current and emerging diagnostic techniques.

Conclusions:

• Understanding the epidemiology and resistance mechanisms is crucial for effective TKI therapy.
• Accurate molecular diagnosis is essential for patient stratification and treatment selection.
• Continued research into diagnostic strategies and resistance pathways will improve outcomes.