The role of hypoxia in pancreatic cancer: a potential therapeutic target?

被引：141

作者：

Erkan, Mert ^{[1
]}

Kurtoglu, Metin ^{[2
]}

Kleeff, Jorg ^{[3
,4
]}

机构：

[1] Koc Univ, Sch Med, Dept Surg, Istanbul, Turkey

[2] Koc Univ, Sch Med, Dept Oncol, Istanbul, Turkey

[3] Royal Liverpool & Broadgreen Univ Hosp, Dept Surg, Liverpool, Merseyside, England

[4] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept General Visceral & Pediat Surg, Dusseldorf, Germany

来源：

EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY | 2016年 / 10卷 / 03期

关键词：

PEGPH20; Pancreatic cancer; desmoplasia; metabolism; hypoxia; cancer stem cell; epithelial-to-mesenchymal transition; TH-302; EPITHELIAL-MESENCHYMAL TRANSITION; REDUCTIVE GLUTAMINE-METABOLISM; MTOR INHIBITOR EVEROLIMUS; INDUCIBLE FACTOR-1-ALPHA; CELL-DEATH; STELLATE CELLS; SUPEROXIDE-DISMUTASE; ALPHA-KETOGLUTARATE; PROGNOSTIC MARKER; UP-REGULATION;

D O I：

10.1586/17474124.2016.1117386

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

One of the key factors that correlates with poor survival of patients with pancreatic cancer is the extent of hypoxic areas within the tumor tissue. The adaptation of pancreatic cancer cells to limited oxygen delivery promotes the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development, which resist in most cases adjuvant therapies following tumor resection. In this article, the authors summarize the evidence demonstrating the significance of hypoxia in pancreatic cancer pathogenesis and discuss the possible hypoxia-induced mechanisms underlying its aggressive nature. We then conclude with promising strategies that target hypoxia-adapted pancreatic cancer cells.

引用

页码：301 / 316

页数：16

共 134 条

[1]

Upregulation of BNIP3 by 5-aza-2′-deoxycytidine sensitizes pancreatic cancer cells to hypoxia-mediated cell death [J].

Abe, T ;

Toyota, M ;

Suzuki, H ;

Murai, M ;

Akino, K ;

Ueno, M ;

Nojima, M ;

Yawata, A ;

Miyakawa, H ;

Suga, T ;

Ito, H ;

Endo, T ;

Tokino, T ;

Hinoda, Y ;

Imai, K .

JOURNAL OF GASTROENTEROLOGY, 2005, 40 (05) :504-510

[2]

Abraham RT, 2003, CURR TOP MICROBIOL, V279, P299

[3]

Akakura N, 2001, CANCER RES, V61, P6548

[4]

Unraveling the therapeutic potential of the Hedgehog pathway in cancer [J].

Amakye, Dereck ;

Jagani, Zainab ;

Dorsch, Marion .

NATURE MEDICINE, 2013, 19 (11) :1410-1422

[5]

[Anonymous], J CLIN ONCOL S

[6]

An Undesired Effect of Chemotherapy GEMCITABINE PROMOTES PANCREATIC CANCER CELL INVASIVENESS THROUGH REACTIVE OXYGEN SPECIES-DEPENDENT, NUCLEAR FACTOR κB- AND HYPOXIA-INDUCIBLE FACTOR 1α-MEDIATED UP-REGULATION OF CXCR4 [J].

Arora, Sumit ;

Bhardwaj, Arun ;

Singh, Seema ;

Srivastava, Sanjeev K. ;

McClellan, Steven ;

Nirodi, Chaitanya S. ;

Piazza, Gary A. ;

Grizzle, William E. ;

Owen, Laurie B. ;

Singh, Ajay P. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (29) :21197-21207

[7]

Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells [J].

Bachem, MG ;

Schünemann, M ;

Ramadani, M ;

Siech, M ;

Beger, H ;

Buck, A ;

Zhou, SX ;

Schmid-Kotsas, A ;

Adler, G .

GASTROENTEROLOGY, 2005, 128 (04) :907-921

[8]

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors [J].

Birsoy, Kivanc ;

Wang, Tim ;

Possemato, Richard ;

Yilmaz, Omer H. ;

Koch, Catherine E. ;

Chen, Walter W. ;

Hutchins, Amanda W. ;

Gultekin, Yetis ;

Peterson, Tim R. ;

Carette, Jan E. ;

Brummelkamp, Thijn R. ;

Clish, Clary B. ;

Sabatini, David M. .

NATURE GENETICS, 2013, 45 (01) :104-U149

[9]

Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer [J].

Borad, Mitesh J. ;

Reddy, Shantan G. ;

Bahary, Nathan ;

Uronis, Hope E. ;

Sigal, Darren ;

Cohn, Allen L. ;

Schelman, William R. ;

Stephenson, Joe, Jr. ;

Chiorean, E. Gabriela ;

Rosen, Peter J. ;

Ulrich, Brian ;

Dragovich, Tomislav ;

Del Prete, Salvatore A. ;

Rarick, Mark ;

Eng, Clarence ;

Kroll, Stew ;

Ryan, David P. .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (13) :1475-1481

[10]

Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia [J].

Bruick, RK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (16) :9082-9087

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