UNLABELLED: Half of patients with KRAS wild-type colorectal cancer do not benefit from adding anti-epithelial growth factor receptor (EGFR) to standard chemotherapy regimens. This retrospective study was performed in 94 patients with metastatic colorectal cancer (mCRC) treated in the second line with cetuximab and chemotherapy. Signal transducer and activator of transcription 3 (STAT3) phosphorylation in tumor cells was correlated with decreased median progression-free survival and overall survival (OS). These results highlight the potential role of STAT3 as a molecular target to optimize anti-EGFR therapies. BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is involved in epithelial growth factor receptor (EGFR) signaling in a KRAS-independent manner. Phosphorylated STAT3 (pSTAT3) expression in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR-containing salvage chemotherapy has never been investigated. PATIENTS AND METHODS: : The first endpoint of this retrospective study was to evaluate the impact of pSTAT3 on the time to progression (TTP) in 94 patients with mCRC treated with anti-EGFR-based therapies in the second- or third-line setting between July 2004 and November 2009. The influence of pSTAT3 on objective response rate and overall survival (OS) was also reported. Nuclear expression of pSTAT3 status was evaluated by immunohistochemical tests on formalin-fixed and paraffin-embedded tumor samples obtained before therapy. RESULTS: Positive expression of pSTAT3 was observed in 24.5% of the tumor samples. The probability of achieving an objective response was 13% among patients with positive nuclear expression of pSTAT3 compared with 41% for patients displaying pSTAT3-negative tumors (P = .02). In a multivariate logistic regression model, high-grade skin rash, wild-type KRAS status, and negative pSTAT3 status significantly improved TTP and OS. CONCLUSION: These results underscore an impact of pSTAT3 on the clinical efficacy of anti-EGFR-containing chemotherapy regimens and support the prospective assessment of this biomarker.
UNLABELLED: Half of patients with KRAS wild-type colorectal cancer do not benefit from adding anti-epithelial growth factor receptor (EGFR) to standard chemotherapy regimens. This retrospective study was performed in 94 patients with metastatic colorectal cancer (mCRC) treated in the second line with cetuximab and chemotherapy. Signal transducer and activator of transcription 3 (STAT3) phosphorylation in tumor cells was correlated with decreased median progression-free survival and overall survival (OS). These results highlight the potential role of STAT3 as a molecular target to optimize anti-EGFR therapies. BACKGROUND:Signal transducer and activator of transcription 3 (STAT3) is involved in epithelial growth factor receptor (EGFR) signaling in a KRAS-independent manner. Phosphorylated STAT3 (pSTAT3) expression in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR-containing salvage chemotherapy has never been investigated. PATIENTS AND METHODS: : The first endpoint of this retrospective study was to evaluate the impact of pSTAT3 on the time to progression (TTP) in 94 patients with mCRC treated with anti-EGFR-based therapies in the second- or third-line setting between July 2004 and November 2009. The influence of pSTAT3 on objective response rate and overall survival (OS) was also reported. Nuclear expression of pSTAT3 status was evaluated by immunohistochemical tests on formalin-fixed and paraffin-embedded tumor samples obtained before therapy. RESULTS: Positive expression of pSTAT3 was observed in 24.5% of the tumor samples. The probability of achieving an objective response was 13% among patients with positive nuclear expression of pSTAT3 compared with 41% for patients displaying pSTAT3-negative tumors (P = .02). In a multivariate logistic regression model, high-grade skin rash, wild-type KRAS status, and negative pSTAT3 status significantly improved TTP and OS. CONCLUSION: These results underscore an impact of pSTAT3 on the clinical efficacy of anti-EGFR-containing chemotherapy regimens and support the prospective assessment of this biomarker.
Authors: Nelson Ung; Tracy L Putoczki; Stanley S Stylli; Irvin Ng; John M Mariadason; Timothy A Chan; Hong-Jian Zhu; Rodney B Luwor Journal: Cancer Biol Ther Date: 2014-02-20 Impact factor: 4.742
Authors: Wei Wen; Jun Wu; Lucy Liu; Yan Tian; Ralf Buettner; Meng-Yin Hsieh; David Horne; Thanh H Dellinger; Ernest S Han; Richard Jove; John H Yim Journal: Mol Cancer Date: 2015-05-01 Impact factor: 27.401
Authors: Deepak Vangala; Swetlana Ladigan; Sven T Liffers; Soha Noseir; Abdelouahid Maghnouj; Tina-Maria Götze; Berlinda Verdoodt; Susanne Klein-Scory; Laura Godfrey; Martina K Zowada; Mario Huerta; Daniel L Edelstein; Jaime Martinez de Villarreal; Miriam Marqués; Jörg Kumbrink; Andreas Jung; Tobias Schiergens; Jens Werner; Volker Heinemann; Sebastian Stintzing; Doris Lindoerfer; Ulrich Mansmann; Michael Pohl; Christian Teschendorf; Christiane Bernhardt; Heiner Wolters; Josef Stern; Selami Usta; Richard Viebahn; Jacob Admard; Nicolas Casadei; Stefan Fröhling; Claudia R Ball; Jens T Siveke; Hanno Glimm; Andrea Tannapfel; Wolff Schmiegel; Stephan A Hahn Journal: Genome Med Date: 2021-07-16 Impact factor: 11.117