KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine.

Background: Our previous proteomic study demonstrated that expression of heat shock protein 27 (HSP27) is upregulated in gemcitabine (GEM)-resistant pancreatic cancer cells and that it suppressed the cytotoxic effect of GEM on the cells. This report describes the benefits of a treatment strategy combining the HSP inhibitor KNK437 with GEM for GEM-resistant pancreatic cancer cells.

Methods: We used 2 human pancreatic cancer cell lines, GEM-sensitive KLM1 and GEM-resistant KLM1-R.

A proteomic profiling of gemcitabine resistance in pancreatic cancer cell lines.

Pancreatic cancer is one of the most highly fatal cancers and is generally resistant to chemotherapy. Currently, gemcitabine appears to be the only effective agent for its treatment and is the preferred first-line therapy. However, the clinical impact of gemcitabine remains modest due to a high level of inherent and acquired tumor resistance.

Proteomics finding heat shock protein 27 as a biomarker for resistance of pancreatic cancer cells to gemcitabine.

Pancreatic cancer remains a devastating disease and >96% of patients with pancreatic cancer do not survive for more than 5 years. Gemcitabine (2'-deoxy-2'-difluoro-deoxycytidine: Gemzar) appears to be the only clinically effective drug for pancreatic cancer, but it has little impact on outcome. Proteomic analysis of gemcitabine-sensitive cells (KLM1) and resistant pancreatic cells (KLM1-R) was performed to identify target proteins of the gemcitabine.