Acquired resistance of pancreatic cancer cells to treatment with gemcitabine and HER-inhibitors is accompanied by increased sensitivity to STAT3 inhibition

International Journal of Oncology
Nikolaos IoannouHelmout Modjtahedi

Abstract

Drug-resistance is a major contributing factor for the poor prognosis in patients with pancreatic cancer. We have shown previously that the irreversible ErbB family blocker afatinib, is more effective than the reversible EGFR tyrosine kinase inhibitor erlotinib in inhibiting the growth of human pancreatic cancer cells. The aim of this study was to develop human pancreatic cancer cell (BxPc3) variants with acquired resistance to treatment with gemcitabine, afatinib, or erlotinib, and to investigate the molecular changes that accompany the acquisition of a drug-resistant phenotype. We also investigated the therapeutic potential of various agents in the treatment of such drug-resistant variants. Three variant forms of BxPc3 cells with acquired resistance to gemcitabine (BxPc3GEM), afatinib (BxPc3AFR) or erlotinib (BxPc3OSIR) were developed following treatment with increasing doses of such drugs. The expression level, mutational and phosphorylation status of various growth factor receptors and downstream cell signaling molecules were determined by FACS, human phopsho-RTK array, and western blot analysis while the sulforhodamine B assay was used for determining the effect of various agents on the growth of such tumours. We found tha...Continue Reading

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Citations

Feb 3, 2018·Assay and Drug Development Technologies·Wei HuangRuo-Pan Huang
Sep 6, 2019·Molecular Biology Reports·Arkadiusz GzilŁukasz Szylberg
May 8, 2018·Oncotarget·Gustavo A Arias-PinillaHelmout Modjtahedi
Jun 29, 2017·Cellular and Molecular Life Sciences : CMLS·Jérémy NigriRichard Tomasini
May 26, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sarrah L HasanaliVinata B Lokeshwar
Aug 29, 2021·Cancer Metastasis Reviews·Kalyani PatilShahab Uddin

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Methods Mentioned

BETA
flow cytometry
ELISA

Clinical Trials Mentioned

NCT02155465
NCT02145637

Software Mentioned

Ion Reporter
Stattic
GraphPad
NextGENe
GraphPad prism
CellQuest Pro
view
Calcusyn

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