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Tissue Cell. 2018 Jun;52:124-128. doi: 10.1016/j.tice.2018.05.003. Epub 2018 May 5.

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

Author information

1
AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, 92111, USA; Department of Surgery, University of California, San Diego, CA, 92093, USA; Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, 980-8574, Japan.
2
AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, 92111, USA; Department of Surgery, University of California, San Diego, CA, 92093, USA.
3
Department of Surgery, University of California, San Diego, CA, 92093, USA.
4
Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA. Electronic address: singhshr@mail.nih.gov.
5
Department of Surgery, University of California, San Diego, CA, 92093, USA. Electronic address: bclary@ucsd.edu.
6
Department of Surgery, University of California, San Diego, CA, 92093, USA. Electronic address: mbouvet@ucsd.edu.
7
Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, 980-8574, Japan. Electronic address: m_unno@surg1.med.tohoku.ac.jp.
8
AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, 92111, USA; Department of Surgery, University of California, San Diego, CA, 92093, USA. Electronic address: all@anticancer.com.

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.

KEYWORDS:

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

PMID:
29857821
DOI:
10.1016/j.tice.2018.05.003
[Indexed for MEDLINE]

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