DNA damage response signatures are associated with frontline chemotherapy response and routes of tumor evolution in extensive stage small cell lung cancer.

ABSTRACT:

Introduction

A hallmark of small cell lung cancer (SCLC) is its recalcitrance to therapy. While most SCLCs respond to frontline therapy, resistance inevitably develops. Identifying phenotypes potentiating chemoresistance and immune evasion is a crucial unmet need. Previous reports have linked upregulation of the DNA damage response (DDR) machinery to chemoresistance and immune evasion across cancers. However, it is unknown if SCLCs exhibit distinct DDR phenotypes.

Methods

To study SCLC DDR phenotypes, we developed a new DDR gene analysis method and applied it to SCLC clinical samples, in vitro, and in vivo model systems. We then investigated how DDR regulation is associated with SCLC biology, chemotherapy response, and tumor evolution following therapy.

Results

Using

SUBMITTER: Morris BB 

PROVIDER: S-EPMC11924755 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature