# Acquired MTAP Loss Following Entrectinib Resistance in ROS1‐Rearranged NSCLC With CD74 Exon 3–ROS1 Exon 34 Fusion

## TL;DR

A patient with ROS1-rearranged lung cancer developed resistance to entrectinib, linked to acquired MTAP loss despite no known resistance mutations.

## Contribution

Identifies MTAP loss as a novel resistance mechanism in ROS1-rearranged NSCLC following entrectinib treatment.

## Key findings

- Acquired MTAP loss was observed in a ROS1-rearranged NSCLC patient after entrectinib resistance.
- The CD74–ROS1 fusion remained unchanged, with no known resistance mutations detected.
- Longitudinal genomic profiling is critical for understanding resistance mechanisms and treatment decisions.

## Abstract

This case highlights acquired MTAP loss during disease progression in ROS1‐rearranged NSCLC. Despite persistent CD74–ROS1 fusion and absence of known resistance mutations, the patient developed CNS progression after entrectinib, underscoring the value of longitudinal genomic profiling in guiding treatment decisions.