Galanin 2 Receptor: A Novel Target for a Subset of Pancreatic Ductal Adenocarcinoma

Abstract

Galanin is a 30 amino acid peptide that stimulates three subtype receptors (GAL1–3R). M89b is a lanthionine-stabilized, C-terminally truncated galanin analog that specifically stimulates GAL2R. We investigated the potential of M89b as a therapeutic for pancreatic ductal adenocarcinoma (PDAC) and assessed its safety. The anti-tumor activity of subcutaneously injected M89b on the growth of patient-derived xenografts of PDAC (PDAC–PDX) in mice was investigated. In addition, the safety of M89b was assessed in vitro using a multi-target panel to measure the off-target binding and modulation of enzyme activities. In a PDAC–PDX with a high GAL2R expression, M89b completely inhibited the growth of the tumor (p GAL2R expression, low or negligeable inhibition of tumor growth was measured, and in the PDX without GAL2R expression no influence on the tumor growth was observed. The M89b treatment of the GAL2R high-PDAC–PDX-bearing mice led to a reduction in the expression of RacGap1 (p PCNA (p MMP13 (p 2R is a safe and valuable target for treating PDACs with high GAL2R expression.

Keywords

• galanin
• galanin receptor
• pancreatic ductal adenocarcinoma
• lanthi-galanin
• targeted treatment