LINC01235 Promotes Clonal Evolution through DNA Replication Licensing-Induced Chromosomal Instability in Breast Cancer.

ABSTRACT: Despite the development of HER2-targeting drugs such as trastuzumab and T-DXd, treatment resistance is a substantial challenge, often leading to relapse and distant metastasis. Tumor heterogeneity in HER2-positive breast cancer drives the evolution of resistant clones following therapeutic stress. However, the targetable drivers of anti-HER2 treatment resistance are not thoroughly identified. This study aims to use neoadjuvant-targeted therapy cohorts and a patient-derived organoid in vitro treatment model to uncover the potential targetable drivers of anti-HER2 treatment resistance. it is found that LINC01235 significantly enhances DNA replication licensing and chromosomal instability, fostering clonal expansion and evolution, and ultimately increasing resistance to therapeutic interventi

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC11984920 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature