MEK inhibitor trametinib in combination with gemcitabine regresses a patient-derived orthotopic xenograft (PDOX) pancreatic cancer nude mouse model

Kei Kawaguchi, Kentaro Igarashi, Kentaro Miyake, Thinzar M. Lwin, Masuyo Miyake, Tasuku Kiyuna, Ho Kyoung Hwang, Takashi Murakami, Jonathan C. Delong, Shree Ram Singh, Bryan Clary, Michael Bouvet, Michiaki Unno, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Pancreatic cancer is resistant to treatment and needs precision individualized therapy to improve the outcome of this disease. Previously, we demonstrated that trametinib (TRA), a MEK inhibitor, could inhibit a pancreatic cancer patient-derived orthotopic xenograft (PDOX). In the present study, we show that gemcitabine (GEM) in combination with TRA was more effective than TRA alone. We implanted a patient pancreatic cancer orthotopically in the pancreatic tail of nude mice to establish the PDOX model. After seven weeks of tumor growth, we divided 32 pancreatic-cancer PDOX nude mice into 4 groups of eight: untreated control; GEM (once a week for 2 weeks); TRA (14 consecutive days); GEM + TRA (GEM: once a week for 2 weeks, TRA:14 consecutive days). We found that treated mice on day 14 had significantly reduced tumor volume in comparison to untreated control. TRA and the combination of GEM + TRA therapy significantly inhibited tumor development in comparison to GEM alone. However, GEM + TRA inhibited the PDOX tumor growth significantly greater than TRA alone. These results suggest the clinical potential of the combination of TRA and GEM for pancreatic cancer.

Original languageEnglish
Pages (from-to)124-128
Number of pages5
JournalTissue and Cell
Volume52
DOIs
Publication statusPublished - 2018 Jun
Externally publishedYes

Keywords

  • Cancer resistance
  • Combination
  • Gemcitabine
  • Indvidualized therapy
  • PDOX
  • Pancreatic cancer
  • Precision medicine
  • Trametinib

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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