Supplementary Table 1 from Erlotinib Prolongs Survival in Pancreatic Cancer by Blocking Gemcitabine-Induced MAPK Signals

Miyabayashi, Koji; Ijichi, Hideaki; Mohri, Dai; Tada, Motohisa; Yamamoto, Keisuke; Asaoka, Yoshinari; Ikenoue, Tsuneo; Tateishi, Keisuke; Nakai, Yousuke; Isayama, Hiroyuki; Morishita, Yasuyuki; Omata, Masao; Moses, Harold L.; Koike, Kazuhiko

doi:10.1158/0008-5472.22399856.v1

00085472can121453-sup-supplementary_table_1_pdf_file_-_108k.pdf (108.06 kB)

Supplementary Table 1 from Erlotinib Prolongs Survival in Pancreatic Cancer by Blocking Gemcitabine-Induced MAPK Signals

journal contribution

posted on 2023-03-30, 22:10 authored by Koji Miyabayashi, Hideaki Ijichi, Dai Mohri, Motohisa Tada, Keisuke Yamamoto, Yoshinari Asaoka, Tsuneo Ikenoue, Keisuke Tateishi, Yousuke Nakai, Hiroyuki Isayama, Yasuyuki Morishita, Masao Omata, Harold L. Moses, Kazuhiko Koike

Supplementary Table 1 PDF file - 108K, Adding erlotinib to gemcitabine synergistically inhibited the growth of mouse and human PDAC cells

History

ARTICLE ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. Although many regimens have been used for PDAC treatment, the combination of the EGF receptor (EGFR) inhibitor erlotinib with gemcitabine has been the only molecular-targeted drug tested so far that has been superior to gemcitabine alone. The mechanism underlying this effective combinational regimen remains unknown. Here, we show that the combination is superior to gemcitabine alone in blocking progression and prolonging survival in a murine model of PDAC (Kras activation with Tgfbr2 knockout). We found that gemcitabine induced mitogen-activated protein kinase signaling, which was dramatically inhibited by erlotinib even in the Kras-activated PDAC cells in the mouse model. Mechanistic investigations suggested that gemcitabine induces EGFR ligand expression and ERBB2 activation by increasing heterodimer formation with EGFR, thereby maintaining high levels of ERBB2 protein in PDAC cells. Overall, our findings suggest a significant role of ERBB in PDAC treatment. Cancer Res; 73(7); 2221–34. ©2013 AACR.