Data from STAT3/IRF1 Pathway Activation Sensitizes Cervical Cancer Cells to Chemotherapeutic Drugs

• DOI: 10.1158/0008-5472.c.6507872
• Publication Date: 2023-04-01T01:47:51Z
• Authors: Barbara Walch-Rüc...; Jennifer Pahne-Ze...; Jil Fischbach; Claudia Wickenhauser; Lars Christian Horn; Lars Tharun; Reinhard Büttner; Peter Mallmann; Peter Stern; Yoo-Jin Kim; Rainer Maria Bohle; Christian Rübe; Russalina Ströder; Ingolf Juhasz-Böss; Erich-Franz Solom...; Sigrun Smola
• Keywords: IRF1

<div>Abstract<p>Neoadjuvant radio/chemotherapy regimens can markedly improve cervical cancer outcome in a subset of patients, while other patients show poor responses, but may encounter severe adverse effects. Thus, there is strong need for predictive biomarkers to clinical management patients. STAT3 considered as critical antiapoptotic factor various malignancies. We therefore investigated activation during carcinogenesis and its impact on the response cells chemotherapeutic drugs. Tyr705-phosphorylated increased from low-grade intraepithelial neoplasia (CIN1) precancerous CIN3 lesions. Notably, pTyr705-STAT3 significantly declined invasive cancer, also when compared same biopsy. was low or absent cultured human cell lines, consistent with <i>in vivo</i> expression data. Unexpectedly, IL6-type cytokine signaling inducing rendered more susceptible drugs, that is, cisplatin etoposide. This chemosensitization STAT3-dependent we identified IFN regulatory factor-1 (IRF1) STAT3-inducible mediator required death enhancement. In line these data, correlated nuclear IRF1 vivo</i>. Importantly, high pretreatment biopsy associated better neoadjuvant summary, our study has key role STAT3/IRF1 pathway cancer. Our results suggest pretherapeutic should be evaluated novel biomarker responses. <i>Cancer Res; 76(13); 3872–83. ©2016 AACR</i>.</p></div>