Therapeutic Potential for FGFR Inhibitors in SOX9-FGFR2 Coexpressing Pancreatic Cancer

Deciphering role of FGFR signalling pathway in pancreatic cancer

“…Several FGFR inhibitors have been discovered for potential treatment of human cancers including pancreatic cancer 96 (Table 1). For example, SSR128129E is an orally effective allosteric FGFR inhibitor, which has no effect on other related RTKs.…”

Fibroblast Growth Factor 10 in Pancreas Development and Pancreatic Cancer

“…These studies further consolidate SOX9 as a central player in pancreatic adenocarcinoma via promoting ADM, particularly in the context of oncogenic KRAS and pancreatitis to accelerate development of premalignant lesions and PDAC (Figure 2 ). Therefore, three positive feedback loops have emerged from these studies (Figure 2 ): (1) FGF10/FGFR2/SOX9 inter-dependent expression is also present in a subset of PDAC patients ( Seymour et al, 2012 ; O’Sullivan et al, 2017 ); (2) EGFR, via activation of NFATC1 and NFATC4, promotes SOX9 expression, whereas activated SOX9 stimulates ERBB2 protein expression ( Chen et al, 2015 ; Grimont et al, 2015 ; Hessmann et al, 2016 ); (3) Oncogenic KRAS via TAK1/NF-κβ promotes SOX9 expression/activation, and SOX9 in turn enhances NF-κβ activity ( Zhou et al, 2018 ). These findings open new perspectives for precision therapeutic strategies targeting specific cancer-driven signaling molecules such as ERBB2 or FGFR2.…”