MEK inhibitor trametinib in combination with gemcitabine regresses a patient-derived orthotopic xenograft (PDOX) pancreatic cancer nude mouse model. (June 2018)

• Record Type: Journal Article
• Authors: Kawaguchi, Kei; Igarashi, Kentaro; Miyake, Kentaro; Lwin, Thinzar M.; Miyake, Masuyo; Kiyuna, Tasuku; Hwang, Ho Kyoung; Murakami, Takashi; Delong, Jonathan C.; Singh, Shree Ram; Clary, Bryan; Bouvet, Michael; Unno, Michiaki; Hoffman, Robert M.
• Is Part Of: Tissue & cell. Volume 52(2018)
• Page Start: 124
• Page End: 128
• Publication Date: 2018-06
• Subjects: Pancreatic cancer -- PDOX -- Trametinib -- Gemcitabine -- Combination -- Cancer resistance -- Indvidualized therapy -- Precision medicine; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2018.05.003
• Languages: English
• ISSNs: 0040-8166

Abstract

Highlights: Combination of GEM and TRA seems to have great promise for pancreatic cancer. Acute toxicity was not associated with the strong efficacy of GEM and TRA. High level of tumor necrosis and fibrosis was observed in the combination therapy. 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.