Verteporfin‐based photodynamic therapy overcomes gemcitabine insensitivity in a panel of pancreatic cancer cell lines

Pancreatic cancer is notoriously difficult to treat and resistant to virtually all therapeutics including gemcitabine, the standard front line agent for palliative chemotherapy. Early clinical studies point to a potential role for photodynamic therapy (PDT) in the management of this deadly disease. Here we examine PDT with verteporfin for treatment of cells that are nonresponsive to gemcitabine and identify intracellular and extracellular factors that govern sensitivity to each modality.

[1]  Pierre Michel,et al.  FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. , 2011, The New England journal of medicine.

[2]  David A. Cheresh,et al.  Integrins in cancer: biological implications and therapeutic opportunities , 2010, Nature Reviews Cancer.

[3]  Malte Buchholz,et al.  Stromal biology and therapy in pancreatic cancer , 2010, Gut.

[4]  Tayyaba Hasan,et al.  Quantitative imaging reveals heterogeneous growth dynamics and treatment-dependent residual tumor distributions in a three-dimensional ovarian cancer model. , 2010, Journal of biomedical optics.

[5]  Bryan Q. Spring,et al.  Imaging and photodynamic therapy: mechanisms, monitoring, and optimization. , 2010, Chemical reviews.

[6]  David Allard,et al.  Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer , 2009, Science.

[7]  Stephen P. Pereira,et al.  Photodynamic therapy for pancreatic and biliary tract carcinoma , 2009, BiOS.

[8]  D. Kessel Promotion of PDT Efficacy by a Bcl‐2 Antagonist , 2008, Photochemistry and photobiology.

[9]  Jinming Gao,et al.  Theranostic nanomedicine for cancer. , 2008, Nanomedicine.

[10]  D. Kessel,et al.  Apoptotic and autophagic responses to Bcl-2 inhibition and photodamage , 2007, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[11]  G. Gallick,et al.  Development and Characterization of Gemcitabine-Resistant Pancreatic Tumor Cells , 2007, Annals of Surgical Oncology.

[12]  Gerald C. Chu,et al.  Stromal biology of pancreatic cancer , 2007, Journal of cellular biochemistry.

[13]  C. Gomer,et al.  Survivin, a member of the inhibitor of apoptosis family, is induced by photodynamic therapy and is a target for improving treatment response. , 2007, Cancer research.

[14]  D. V. Von Hoff,et al.  Tumor-stroma interactions in pancreatic ductal adenocarcinoma , 2007, Molecular Cancer Therapeutics.

[15]  T. Okumura,et al.  Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells , 2007, British Journal of Cancer.

[16]  M. Talamonti,et al.  Surgical management of pancreatic cancer. , 2005, Seminars in radiation oncology.

[17]  Jayanta Debnath,et al.  Modelling glandular epithelial cancers in three-dimensional cultures , 2005, Nature Reviews Cancer.

[18]  S. Hirohashi,et al.  Orthotopic Transplantation Models of Pancreatic Adenocarcinoma Derived From Cell Lines and Primary Tumors and Displaying Varying Metastatic Activity , 2004, Pancreas.

[19]  K. Ohuchida,et al.  Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions. , 2004, Cancer research.

[20]  C. Gomer,et al.  The Matrix Metalloproteinase Inhibitor Prinomastat Enhances Photodynamic Therapy Responsiveness in a Mouse Tumor Model , 2004, Cancer Research.

[21]  H. Kalthoff,et al.  Resistance of pancreatic cancer to gemcitabine treatment is dependent on mitochondria‐mediated apoptosis , 2004, International journal of cancer.

[22]  K. Tsuchida,et al.  Tumor-Stroma Interaction of Human Pancreatic Cancer: Acquired Resistance to Anticancer Drugs and Proliferation Regulation Is Dependent on Extracellular Matrix Proteins , 2004, Pancreas.

[23]  M. Löhr,et al.  A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform , 2003, Virchows Archiv.

[24]  R. DePinho,et al.  Pancreatic cancer biology and genetics , 2002, Nature Reviews Cancer.

[25]  C. Gomer,et al.  Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. , 2002, Cancer research.

[26]  Paul M. Ripley,et al.  Photodynamic therapy for cancer of the pancreas , 2002, Gut.

[27]  P. Pour,et al.  Pancreatic Cell Lines: A Review , 2002, Pancreas.

[28]  S. R. Abel,et al.  Verteporfin for Age-Related Macular Degeneration , 2001, The Annals of pharmacotherapy.

[29]  Mina J. Bissell,et al.  Putting tumours in context , 2001, Nature Reviews Cancer.

[30]  Stanley B. Brown,et al.  Verteporfin: a milestone in opthalmology and photodynamic therapy , 2001, Expert opinion on pharmacotherapy.

[31]  J. Mackey,et al.  Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. , 1999, Journal of the National Cancer Institute.

[32]  Michael R Hamblin,et al.  Combination photoimmunotherapy and cisplatin: effects on human ovarian cancer ex vivo. , 1999, Journal of the National Cancer Institute.

[33]  B. McManus,et al.  Early release of mitochondrial cytochrome c and expression of mitochondrial epitope 7A6 with a porphyrin-derived photosensitizer: Bcl-2 and Bcl-xL overexpression do not prevent early mitochondrial events but still depress caspase activity. , 1999, Laboratory investigation; a journal of technical methods and pathology.

[34]  T. Hasan,et al.  BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and β1 integrin expression in ovarian cancer cells , 1999, British Journal of Cancer.

[35]  B. McManus,et al.  Overexpression of Bcl‐XL prevents caspase‐3‐mediated activation of DNA fragmentation factor (DFF) produced by treatment with the photochemotherapeutic agent BPD‐MA , 1998, FEBS letters.

[36]  D. V. Von Hoff,et al.  Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  T. Hasan,et al.  PHOTOPHYSICAL AND PHOTOSENSITIZING PROPERTIES OF BENZOPORPHYRIN DERIVATIVE MONOACID RING A (BPD‐MA) * , 1994, Photochemistry and photobiology.

[38]  E. Glatstein,et al.  Photodynamic therapy of cancer. , 1988, Comprehensive therapy.

[39]  S. Onda,et al.  [Pancreatic carcinoma]. , 2012, Nihon rinsho. Japanese journal of clinical medicine.

[40]  K. Garber Stromal depletion goes on trial in pancreatic cancer. , 2010, Journal of the National Cancer Institute.

[41]  T. Hasan,et al.  Synergistic Enhancement of Carboplatin Efficacy with Photodynamic Therapy in a Three-Dimensional Model for Micrometastatic Ovarian Cancer , 2010 .

[42]  D. Kessel,et al.  Initiation of autophagy by photodynamic therapy. , 2009, Methods in enzymology.

[43]  D. Kessel,et al.  Photodynamic therapy: A mitochondrial inducer of apoptosis , 1999, Cell Death and Differentiation.

[44]  R. Bold,et al.  Gemcitabine-Induced Programmed Cell Death (Apoptosis) of Human Pancreatic Carcinoma Is Determined by Bcl-2 Content , 1999, Annals of Surgical Oncology.

[45]  M Pauer,et al.  Photodynamic therapy for gastrointestinal tumors using three photosensitizers--ALA induced PPIX, Photofrin and MTHPC. A pilot study. , 1998, Neoplasma.

[46]  H. Messman,et al.  Photodynamic therapy of a transplanted pancreatic cancer model using meta-tetrahydroxyphenylchlorin (mTHPC). , 1997, British Journal of Cancer.

[47]  T. Dougherty Photodynamic therapy. , 1993, Photochemistry and photobiology.