Preclinical study and parallel phase II trial evaluating antisense STAT3 oligonucleotide and checkpoint blockade for advanced pancreatic, non-small cell lung cancer and mismatch repair-deficient colorectal cancer.

ABSTRACT:

Objective

To evaluate signal transducer and activator of transcription 3 (STAT3) inhibition we conducted a co-clinical trial testing danvatirsen, a STAT3 antisense oligonucleotide (ASO) and checkpoint inhibition in conjunction with preclinical experiments.

Methods and analysis

Orthotopically implanted pancreatic cancer (pancreatic adenocarcinoma (PDAC)) was treated with STAT3 ASO with immune checkpoint inhibition. Tumour infiltrating immune cell populations were characterised via flow cytometry. In vitro experiments evaluated STAT3 inhibition in pancreatic stellate cells (PSCs) and myeloid-derived suppressor cells (MDSCs).A phase II trial employing a Simon II stage design tested the clinical efficacy of danvatirsen and durvalumab in non-small cell lung cancer (NSCLC), PDAC a

SUBMITTER: Tang C 

PROVIDER: S-EPMC11347683 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature