A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade.

ABSTRACT:

Purpose

Small cell lung cancer (SCLC) has an extremely poor prognosis. Despite high initial response rates to chemotherapy and modest survival improvements with the addition of immune checkpoint inhibitors (ICI), almost all patients experience relapse and fatal outcomes. Recent genomic insights uncovered extensive molecular heterogeneity in addition to the almost uniform loss of RB1 and TRP53. Additionally, defective DNA mismatch repair (MMR) has recently been described in some SCLC cases. Here, we generated a novel SCLC mouse model capturing MMR deficiency and assessed immunotherapy responses.

Methods

We developed an MMR-deficient genetically engineered mouse model (GEMM) of SCLC by introducing a conditional Msh2 gene, crucial for maintaining MMR integrity, into the standar

SUBMITTER: Ibruli O 

PROVIDER: S-EPMC11564195 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature