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Tumor Microenvironment as a Determinant of Photodynamic Therapy Resistance

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Resistance to Photodynamic Therapy in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 5))

Abstract

The tumor microenvironment is a complex force to be reckoned with in terms of cancer treatment. Structure and composition of the tumor stroma, oxygenation status within the tumor, and expression and/or activation of proteins that mediate tumor progression can contribute to the efficacy of, or resistance to, various therapeutic modalities. Photodynamic therapy (PDT) is no exception—the oxygenation status and molecular makeup of the tumor and its stroma is critically important to the success of PDT. Moreover, the application of light therapy to a tumor can counteract the therapeutic benefit by altering the microenvironment. For example, PDT is capable of inducing hypoxia which can limit the extent of PDT damage (by consuming oxygen too rapidly), initiating angiogenesis which allows for reestablishment of the tumor vasculature, and activating survival signaling pathways and increasing expression of proteins which promote tumor progression. This chapter highlights key players in the tumor microenvironment that contribute to treatment failure as well as how resistance can be circumvented by overcoming these road blocks. Further, this chapter will discuss various technologies developed to monitor the tumor microenvironment in an effort to improve PDT dosimetry, allowing for personalized treatment that increases therapeutic efficacy.

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References

  1. Fukumura D, Duda DG, Munn LL, Jain RK. Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation. 2010;17:206–25.

    PubMed Central  CAS  PubMed  Google Scholar 

  2. Provenzano PP, Hingorani SR. Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer. Br J Cancer. 2013;108:1–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Fokas E, McKenna WG, Muschel RJ. The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies. Cancer Metastasis Rev. 2012;31:823–42.

    CAS  PubMed  Google Scholar 

  4. Busch TM. Local physiological changes during photodynamic therapy. Lasers Surg Med. 2006;38:494–99.

    PubMed  Google Scholar 

  5. Ishikawa T, Kajimoto Y, Sun W, Nakagawa H, Inoue Y, Ikegami Y, Miyatake S, Kuroiwa T. Role of Nrf2 in cancer photodynamic therapy: regulation of human ABC transporter ABCG2. J Pharm Sci. 2013;102:3058–69.

    CAS  PubMed  Google Scholar 

  6. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    CAS  PubMed  Google Scholar 

  7. Weis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med. 2011;17:1359–70.

    CAS  PubMed  Google Scholar 

  8. Tomioka Y, Kushibiki T, Awazu K. Evaluation of oxygen consumption of culture medium and in vitro photodynamic effect of talaporfin sodium in lung tumor cells. Photomed Laser Surg. 2010;28:385–90.

    CAS  PubMed  Google Scholar 

  9. Henderson BW, Gollnick SO, Snyder JW, Busch TM, Kousis PC, Cheney RT, Morgan J. Choice of oxygen-conserving treatment regimen determines the inflammatory response and outcome of photodynamic therapy of tumors. Cancer Res. 2004;64:2120–26.

    CAS  PubMed  Google Scholar 

  10. Huang Z, Chen Q, Shakil A, Chen H, Beckers J, Shapiro H, Hetzel FW. Hyperoxygenation enhances the tumor cell killing of photofrin-mediated photodynamic therapy. Photochem Photobiol. 2003;78:496–502.

    CAS  PubMed  Google Scholar 

  11. Busch TM, Wileyto EP, Emanuele MJ, Del Piero F, Marconato L, Glatstein E, Koch CJ. Photodynamic therapy creates fluence rate-dependent gradients in the intratumoral spatial distribution of oxygen. Cancer Res. 2002;62:7273–9.

    CAS  PubMed  Google Scholar 

  12. Henderson BW, Busch TM, Snyder JW. Fluence rate as a modulator of PDT mechanisms. Lasers Surg Med. 2006;38:489–93.

    PubMed  Google Scholar 

  13. Busch TM, Xing X, Yu G, Yodh A, Wileyto EP, Wang HW, Durduran T, Zhu TC, Wang KK. Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to photofrin photodynamic therapy. Photochem Photobiol Sci. 2009;8:1683–93.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Becker TL, Paquette AD, Keymel KR, Henderson BW, Sunar U. Monitoring blood flow responses during topical ALA-PDT. Biomed Opt Express. 2010;2:123–30.

    PubMed Central  PubMed  Google Scholar 

  15. van Leeuwen-van Zaane F, de Bruijn HS, van der Ploeg-van den Heuvel A, Sterenborg HJ, Robinson DJ. The effect of fluence rate on the acute response of vessel diameter and red blood cell velocity during topical 5-aminolevulinic acid photodynamic therapy. Photodiagn Photodyn Ther. 2014;11:71–81.

    Google Scholar 

  16. Seshadri M, Bellnier DA, Vaughan LA, Spernyak JA, Mazurchuk R, Foster TH, Henderson BW. Light delivery over extended time periods enhances the effectiveness of photodynamic therapy. Clin Cancer Res. 2008;14:2796–805.

    PubMed Central  CAS  PubMed  Google Scholar 

  17. Busch TM, Wang HW, Wileyto EP, Yu G, Bunte RM. Increasing damage to tumor blood vessels during motexafin lutetium-PDT through use of low fluence rate. Radiat Res. 2010;174:331–40.

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Francois A, Salvadori A, Bressenot A, Bezdetnaya L, Guillemin F, D’Hallewin MA. How to avoid local side effects of bladder photodynamic therapy: impact of the fluence rate. J Urol. 2013;190:731–6.

    PubMed  Google Scholar 

  19. Yamamoto J, Yamamoto S, Hirano T, Li S, Koide M, Kohno E, Okada M, Inenaga C, Tokuyama T, Yokota N, Terakawa S, Namba H. Monitoring of singlet oxygen is useful for predicting the photodynamic effects in the treatment for experimental glioma. Clin Cancer Res. 2006;12:7132–9.

    CAS  PubMed  Google Scholar 

  20. Angell-Petersen E, Spetalen S, Madsen SJ, Sun CH, Peng Q, Carper SW, Sioud M, Hirschberg H. Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model. J Neurosurg. 2006;104:109–17.

    PubMed  Google Scholar 

  21. Sitnik TM, Hampton JA, Henderson BW. Reduction of tumor oxygenation during and after photodynamic therapy in vivo: effects of fluence rate. Br J Cancer. 1998;77:1386–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Frost GA, Halliday GM, Damian DL. Photodynamic therapy-induced immunosuppression in humans is prevented by reducing the rate of light delivery. J Invest Dermatol. 2011;131:962–8.

    CAS  PubMed  Google Scholar 

  23. Estevez JP, Ascencio M, Colin P, Farine MO, Collinet P, Mordon S. Continuous or fractionated photodynamic therapy? Comparison of three PDT schemes for ovarian peritoneal micrometastasis treatment in a rat model. Photodiagn Photodyn Ther. 2010;7:251–7.

    Google Scholar 

  24. Zilberstein J, Bromberg A, Frantz A, Rosenbach-Belkin V, Kritzmann A, Pfefermann R, Salomon Y, Scherz A. Light-dependent oxygen consumption in bacteriochlorophyll-serine-treated melanoma tumors: on-line determination using a tissue-inserted oxygen microsensor. Photochem Photobiol. 1997;65:1012–9.

    CAS  PubMed  Google Scholar 

  25. Naghavi N, Miranbaygi MH, Sazgarnia A. Simulation of fractionated and continuous irradiation in photodynamic therapy: study the differences between photobleaching and singlet oxygen dose deposition. Australas Phys Eng Sci Med. 2011;34:203–11.

    PubMed  Google Scholar 

  26. Pogue BW, Hasan T. A theoretical study of light fractionation and dose-rate effects in photodynamic therapy. Radiat Res. 1997;147:551–9.

    CAS  PubMed  Google Scholar 

  27. Xiao Z, Halls S, Dickey D, Tulip J, Moore RB. Fractionated versus standard continuous light delivery in interstitial photodynamic therapy of dunning prostate carcinomas. Clin Cancer Res. 2007;13:7496–505.

    CAS  PubMed  Google Scholar 

  28. Middelburg TA, Van Zaane F, De Bruijn HS, Van Der Ploeg-van den Heuvel A, Sterenborg HJ, Neumann HA, De Haas ER, Robinson DJ. Fractionated illumination at low fluence rate photodynamic therapy in mice. Photochem Photobiol. 2010;86:1140–6.

    CAS  PubMed  Google Scholar 

  29. de Vijlder HC, Sterenborg HJ, Neumann HA, Robinson DJ, de Haas ER. Light fractionation significantly improves the response of superficial basal cell carcinoma to aminolaevulinic acid photodynamic therapy: five-year follow-up of a randomized, prospective trial. Acta Derm Venereol. 2012;92:641–7.

    PubMed  Google Scholar 

  30. Curnow A, Haller JC, Bown SG. Oxygen monitoring during 5-aminolaevulinic acid induced photodynamic therapy in normal rat colon. Comparison of continuous and fractionated light regimes. J Photochem Photobiol B. 2000;58:149–55.

    CAS  PubMed  Google Scholar 

  31. van den Boogert J, van Staveren HJ, de Bruin RW, Siersema PD, van Hillegersberg R. Fractionated illumination for oesophageal ALA-PDT: effect on blood flow and PpIX formation. Lasers Med Sci. 2001;16:16–25.

    PubMed  Google Scholar 

  32. Robinson DJ, de Bruijn HS, Star WM, Sterenborg HJ. Dose and timing of the first light fraction in two-fold illumination schemes for topical ALA-mediated photodynamic therapy of hairless mouse skin. Photochem Photobiol. 2003;77:319–23.

    CAS  PubMed  Google Scholar 

  33. Bogaards A, Varma A, Zhang K, Zach D, Bisland SK, Moriyama EH, Lilge L, Muller PJ, Wilson BC. Fluorescence image-guided brain tumor resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development. Photochem Photobiol Sci. 2005;4:438–42.

    CAS  PubMed  Google Scholar 

  34. Attili SK, Lesar A, McNeill A, Camacho-Lopez M, Moseley H, Ibbotson S, Samuel ID, Ferguson J. An open pilot study of ambulatory photodynamic therapy using a wearable low-irradiance organic light-emitting diode light source in the treatment of nonmelanoma skin cancer. Br J Dermatol. 2009;161:170–3.

    CAS  PubMed  Google Scholar 

  35. Cochrane C, Mordon SR, Lesage JC, Koncar V. New design of textile light diffusers for photodynamic therapy. Mater Sci Eng C Mater Biol Appl. 2013;33:1170–5.

    CAS  PubMed  Google Scholar 

  36. Mathews MS, Angell-Petersen E, Sanchez R, Sun CH, Vo V, Hirschberg H, Madsen SJ. The effects of ultra low fluence rate single and repetitive photodynamic therapy on glioma spheroids. Lasers Surg Med. 2009;41:578–84.

    PubMed Central  PubMed  Google Scholar 

  37. Wiegell SR, Skodt V, Wulf HC. Daylight-mediated photodynamic therapy of basal cell carcinomas-an explorative study. J Eur Acad Dermatol Venereol. 2014;28:169–75.

    CAS  Google Scholar 

  38. Wiegell SR, Fabricius S, Gniadecka M, Stender IM, Berne B, Kroon S, Andersen BL, Mork C, Sandberg C, Ibler KS, Jemec GB, Brocks KM, Philipsen PA, Heydenreich J, Haedersdal M, Wulf HC. Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study. Br J Dermatol. 2012;166:1327–32.

    CAS  PubMed  Google Scholar 

  39. Wiegell SR, Wulf HC, Szeimies RM, Basset-Seguin N, Bissonnette R, Gerritsen MJ, Gilaberte Y, Calzavara-Pinton P, Morton CA, Sidoroff A, Braathen LR. Daylight photodynamic therapy for actinic keratosis: an international consensus: International Society for Photodynamic Therapy in Dermatology. J Eur Acad Dermatol Venereol. 2012;26:673–9.

    CAS  PubMed  Google Scholar 

  40. Peng Q, Nesland JM. Effects of photodynamic therapy on tumor stroma. Ultrastruct Pathol. 2004;28:333–40.

    PubMed  Google Scholar 

  41. Lunardi S, Muschel RJ, Brunner TB. The stromal compartments in pancreatic cancer: are there any therapeutic targets? Cancer Lett. 2014;343:147–55.

    CAS  PubMed  Google Scholar 

  42. Pazos M, Nader HB. Effect of photodynamic therapy on the extracellular matrix and associated components. Braz J Med Biol Res. 2007;40:1025–35.

    CAS  PubMed  Google Scholar 

  43. Maas AL, Carter SL, Wileyto EP, Miller J, Yuan M, Yu G, Durham AC, Busch TM. Tumor vascular microenvironment determines responsiveness to photodynamic therapy. Cancer Res. 2012;72:2079–88.

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Fungaloi P, Statius van Eps R, Wu YP, Blankensteijn J, de Groot P, van Urk H, van Hillegersberg R, LaMuraglia G. Platelet adhesion to photodynamic therapy-treated extracellular matrix proteins. Photochem Photobiol. 2002;75:412–7.

    CAS  PubMed  Google Scholar 

  45. Overhaus M, Heckenkamp J, Kossodo S, Leszczynski D, LaMuraglia GM. Photodynamic therapy generates a matrix barrier to invasive vascular cell migration. Circ Res. 2000;86:334–40.

    CAS  PubMed  Google Scholar 

  46. Waterman PR, Overhaus M, Heckenkamp J, Nigri GR, Fungaloi PF, Landis ME, Kossodo SC, LaMuraglia GM. Mechanisms of reduced human vascular cell migration after photodynamic therapy. Photochem Photobiol. 2002;75:46–50.

    CAS  PubMed  Google Scholar 

  47. de Vree WJ, Fontijne-Dorsman AN, Koster JF, Sluiter W. Photodynamic treatment of human endothelial cells promotes the adherence of neutrophils in vitro. Br J Cancer. 1996;73:1335–40.

    PubMed Central  PubMed  Google Scholar 

  48. Kousis PC, Henderson BW, Maier PG, Gollnick SO. Photodynamic therapy enhancement of antitumor immunity is regulated by neutrophils. Cancer Res. 2007;67:10501–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Fungaloi P, Waterman P, Nigri G, Statius-van Eps R, Sluiter W, van Urk H, LaMuraglia G. Photochemically modulated endothelial cell thrombogenicity via the thrombomodulin-tissue factor pathways. Photochem Photobiol. 2003;785:475–80.

    Google Scholar 

  50. Drakopoulou M, Toutouzas K, Michelongona A, Tousoulis D, Stefanadis C. Vulnerable plaque and inflammation: potential clinical strategies. Curr Pharm Des. 2011;17:4190–209.

    CAS  PubMed  Google Scholar 

  51. Egeblad M, Rasch MG, Weaver VM. Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol. 2010;22:697–706.

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Arendt LM, Rudnick JA, Keller PJ, Kuperwasser C. Stroma in breast development and disease. Semin Cell Dev Biol. 2010;21:11–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  53. Rucki AA, Zheng L. Pancreatic cancer stroma: understanding biology leads to new therapeutic strategies. World J Gastroenterol. 2014;20:2237–46.

    PubMed Central  PubMed  Google Scholar 

  54. Shields MA, Dangi-Garimella S, Redig AJ, Munshi HG. Biochemical role of the collagen-rich tumor microenvironment in pancreatic cancer progression. Biochem J. 2012;441:541–52.

    CAS  PubMed  Google Scholar 

  55. Celli JP, Solban N, Liang A, Pereira SP, Hasan T. Verteporfin-based photodynamic therapy overcomes gemcitabine insensitivity in a panel of pancreatic cancer cell lines. Lasers Surg Med. 2011;43:565–74.

    PubMed Central  PubMed  Google Scholar 

  56. Celli JP. Stromal interactions as regulators of tumor growth and therapeutic response: a potential target for photodynamic therapy? Isr J Chem. 2012;52:757–66.

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Hwang RF, Moore T, Arumugam T, Ramachandran V, Amos KD, Rivera A, Ji B, Evans DB, Logsdon CD. Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Res. 2008;68:918–26.

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Garmy-Susini B, Varner JA. Roles of integrins in tumor angiogenesis and lymphangiogenesis. Lymphat Res Biol. 2008;6:155–63.

    PubMed Central  CAS  PubMed  Google Scholar 

  59. Margaron P, Sorrenti R, Levy JG. Photodynamic therapy inhibits cell adhesion without altering integrin expression. Biochim Biophys Acta. 1997;1359:200–10.

    CAS  PubMed  Google Scholar 

  60. Runnels JM, Chen N, Ortel B, Kato D, Hasan T. BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and beta1 integrin expression in ovarian cancer cells. Br J Cancer. 1999;80:946–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  61. Uzdensky AB, Juzeniene A, Kolpakova E, Hjortland GO, Juzenas P, Moan J. Photosensitization with protoporphyrin IX inhibits attachment of cancer cells to a substratum. Biochem Biophys Res Commun. 2004;322:452–7.

    CAS  PubMed  Google Scholar 

  62. Milla LN, Cogno IS, Rodriguez ME, Sanz-Rodriguez F, Zamarron A, Gilaberte Y, Carrasco E, Rivarola VA, Juarranz A. Isolation and characterization of squamous carcinoma cells resistant to photodynamic therapy. J Cell Biochem. 2011;112:2266–78.

    CAS  PubMed  Google Scholar 

  63. Espada J, Galaz S, Sanz-Rodriguez F, Blazquez-Castro A, Stockert JC, Bagazgoitia L, Jaen P, Gonzalez S, Cano A, Juarranz A. Oncogenic H-Ras and PI3K signaling can inhibit E-cadherin-dependent apoptosis and promote cell survival after photodynamic therapy in mouse keratinocytes. J Cell Physiol. 2009;219:84–93.

    CAS  PubMed  Google Scholar 

  64. Galaz S, Espada J, Stockert JC, Pacheco M, Sanz-Rodriguez F, Arranz R, Rello S, Canete M, Villanueva A, Esteller M, Juarranz A. Loss of E-cadherin mediated cell-cell adhesion as an early trigger of apoptosis induced by photodynamic treatment. J Cell Physiol. 2005;205:86–96.

    CAS  PubMed  Google Scholar 

  65. Gomer CJ, Ferrario A, Luna M, Rucker N, Wong S. Photodynamic therapy: combined modality approaches targeting the tumor microenvironment. Lasers Surg Med. 2006;38:516–21.

    PubMed  Google Scholar 

  66. Ortel B, Shea CR, Calzavara-Pinton P. Molecular mechanisms of photodynamic therapy. Front Biosci(Landmark Ed). 2009;14:4157–72.

    CAS  Google Scholar 

  67. Gomer CJ. Induction of prosurvival molecules during treatment: rethinking therapy options for photodynamic therapy. J Natl Compr Cancer Netw. 2012;10:S35–9.

    CAS  Google Scholar 

  68. Casas A, Di Venosa G, Hasan T, Al B. Mechanisms of resistance to photodynamic therapy. Curr Med Chem. 2011;18:2486–515.

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Gilaberte Y, Milla L, Salazar N, Vera-Alvarez J, Kourani O, Damian A, Rivarola V, Jose Roca M, Espada J, Gonzalez S, Juarranz A. Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy. J Invest Dermatol. 2014;134:2428–37. doi:10.1038/jid.2014.178 jid2014178 [pii].

    CAS  PubMed  Google Scholar 

  70. Edmonds C, Hagan S, Gallagher-Colombo SM, Busch TM, Cengel KA. Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: targeting survival pathways to increase PDT efficacy in ovarian and lung cancer. Cancer Biol Ther. 2012;13:1463–70.

    PubMed Central  CAS  PubMed  Google Scholar 

  71. Yang PW, Hung MC, Hsieh CY, Tung EC, Wang YH, Tsai JC, Lee JM. The effects of photofrin-mediated photodynamic therapy on the modulation of EGFR in esophageal squamous cell carcinoma cells. Lasers Med Sci. 2013;28:605–14.

    PubMed  Google Scholar 

  72. Martinez-Carpio PA, Trelles MA. The role of epidermal growth factor receptor in photodynamic therapy: a review of the literature and proposal for future investigation. Lasers Med Sci. 2010;25:767–71.

    PubMed  Google Scholar 

  73. Weyergang A, Selbo PK, Berg K. Sustained ERK [corrected] inhibition by EGFR targeting therapies is a predictive factor for synergistic cytotoxicity with PDT as neoadjuvant therapy. Biochim Biophys Acta. 2013;1830:2659–70.

    CAS  PubMed  Google Scholar 

  74. Zhang H, Shen B, Swinarska JT, Li W, Xiao K, He P. 9-Hydroxypheophorbide alpha-mediated photodynamic therapy induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in Hep-2 cells via ROS-mediated suppression of the ERK pathway. Photodiagn Photodyn Ther. 2014;11:55–62.

    CAS  Google Scholar 

  75. Ferrario A, Fisher AM, Rucker N, Gomer CJ. Celecoxib and NS-398 enhance photodynamic therapy by increasing in vitro apoptosis and decreasing in vivo inflammatory and angiogenic factors. Cancer Res. 2005;65:9473–8.

    CAS  PubMed  Google Scholar 

  76. Ferrario A, Von Tiehl K, Wong S, Luna M, Gomer CJ. Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. Cancer Res. 2002;62:3956–61.

    CAS  PubMed  Google Scholar 

  77. Ferrario A, Gomer CJ. Targeting the 90 kDa heat shock protein improves photodynamic therapy. Cancer Lett. 2010;289:188–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Bhuvaneswari R, Gan YY, Yee KK, Soo KC, Olivo M. Effect of hypericin-mediated photodynamic therapy on the expression of vascular endothelial growth factor in human nasopharyngeal carcinoma. Int J Mol Med. 2007;20:421–8.

    CAS  PubMed  Google Scholar 

  79. Gallagher-Colombo SM, Maas AL, Yuan M, Busch TM. Photodynamic therapy-induced angiogenic signaling: consequences and solutions to improve therapeutic response. Isr J Chem. 2012;52:681–90.

    CAS  Google Scholar 

  80. Solban N, Selbo PK, Sinha AK, Chang SK, Hasan T. Mechanistic investigation and implications of photodynamic therapy induction of vascular endothelial growth factor in prostate cancer. Cancer Res. 2006;66:5633–540.

    CAS  PubMed  Google Scholar 

  81. Thong PS, Olivo M, Kho KW, Bhuvaneswari R, Chin WW, Ong KW, Soo KC. Immune response against angiosarcoma following lower fluence rate clinical photodynamic therapy. J Environ Pathol Toxicol Oncol. 2008;27:35–42.

    CAS  PubMed  Google Scholar 

  82. Bhuvaneswari R, Yuen GY, Chee SK, Olivo. Hypericin-mediated photodynamic therapy in combination with Avastin (bevacizumab) improves tumor response by downregulating angiogenic proteins. Photochem Photobiol Sci. 2007;6:1275–83.

    CAS  PubMed  Google Scholar 

  83. Ferrario A, von Tiehl KF, Rucker N, Schwarz MA, Gill PS, Gomer CJ. Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. Cancer Res. 2000;60:4066–9.

    CAS  PubMed  Google Scholar 

  84. Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366:2–16.

    CAS  PubMed  Google Scholar 

  85. Nyati MK, Morgan MA, Feng FY, Lawrence TS. Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer. 2006;6:876–85.

    CAS  PubMed  Google Scholar 

  86. Abu-Yousif AO, Moor AC, Zheng X, Savellano MD, Yu W, Selbo PK, Hasan T. Epidermal growth factor receptor-targeted photosensitizer selectively inhibits EGFR signaling and induces targeted phototoxicity in ovarian cancer cells. Cancer Lett. 2012;321:120–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  87. Soukos NS, Hamblin MR, Keel S, Fabian RL, Deutsch TF, Hasan T. Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo. Cancer Res. 2001;61:4490–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  88. Bhuvaneswari R, Gan YY, Soo KC, Olivo M. Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response. Mol Cancer. 2009;8:94.

    PubMed Central  PubMed  Google Scholar 

  89. Kim SG, Hong JW, Boo SH, Kim MG, Lee KD, Ahn JC, Hwang HJ, Shin JI, Lee SJ, Oh JK, Chung PS. Combination treatment of Cetuximab and photodynamic therapy in SNU-1041 squamous cancer cell line. Oncol Rep. 2009;22:701–8.

    CAS  PubMed  Google Scholar 

  90. Mir Y, Elrington SA, Hasan T. A new nanoconstruct for epidermal growth factor receptor-targeted photo-immunotherapy of ovarian cancer. Nanomedicine. 2013;9:1114–22.

    PubMed Central  CAS  PubMed  Google Scholar 

  91. Del Carmen MG, Rizvi I, Chang Y, Moor AC, Oliva E, Sherwood M, Pogue B, Hasan T. Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo. J Natl Cancer Inst. 2005;97:1516–24.

    CAS  PubMed  Google Scholar 

  92. Postiglione I, Chiaviello A, Aloj SM, Palumbo G. 5-aminolaevulinic acid/photo-dynamic therapy and gefitinib in non-small cell lung cancer cell lines: a potential strategy to improve gefitinib therapeutic efficacy. Cell Prolif. 2013;46:382–95.

    CAS  PubMed  Google Scholar 

  93. Kim CH, Chung CW, Lee HM, Kim do H, Kwak TW, Jeong YI, Kang DH. Synergistic effects of 5-aminolevulinic acid based photodynamic therapy and celecoxib via oxidative stress in human cholangiocarcinoma cells. Int J Nanomedicine. 2013;8:2173–86.

    PubMed Central  PubMed  Google Scholar 

  94. Bhuvaneswari R, Yuen GY, Chee SK, Olivo M. Antiangiogenesis agents avastin and erbitux enhance the efficacy of photodynamic therapy in a murine bladder tumor model. Lasers Surg Med. 2011;43:651–62.

    PubMed  Google Scholar 

  95. Ferrario A, Gomer CJ. Avastin enhances photodynamic therapy treatment of Kaposi’s sarcoma in a mouse tumor model. J Environ Pathol Toxicol Oncol. 2006;25:251–9.

    CAS  PubMed  Google Scholar 

  96. Jodele S, Chantrain CF, Blavier L, Lutzko C, Crooks GM, Shimada H, Coussens LM, Declerck YA. The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent. Cancer Res. 2005;65:3200–8.

    CAS  PubMed  Google Scholar 

  97. Firczuk M, Nowis D, Golab J. PDT-induced inflammatory and host responses. Photochem Photobiol Sci. 2011;10:653–63.

    CAS  PubMed  Google Scholar 

  98. Ferrario A, Chantrain CF, von Tiehl K, Buckley S, Rucker N, Shalinsky DR, Shimada H, DeClerck YA, Gomer CJ. The matrix metalloproteinase inhibitor prinomastat enhances photodynamic therapy responsiveness in a mouse tumor model. Cancer Res. 2004;64:2328–32.

    CAS  PubMed  Google Scholar 

  99. Barron GA, Moseley H, Woods JA. Differential sensitivity in cell lines to photodynamic therapy in combination with ABCG2 inhibition. J Photochem Photobiol B. 2013;126:87–96.

    CAS  PubMed  Google Scholar 

  100. Morgan J, Jackson JD, Zheng X, Pandey SK, Pandey RK. Substrate affinity of photosensitizers derived from chlorophyll-a: the ABCG2 transporter affects the phototoxic response of side population stem cell-like cancer cells to photodynamic therapy. Mol Pharm. 2010;7:1789–804.

    PubMed Central  CAS  PubMed  Google Scholar 

  101. Robey RW, Steadman K, Polgar O, Bates SE. ABCG2-mediated transport of photosensitizers: potential impact on photodynamic therapy. Cancer Biol Ther. 2005;4:187–94.

    CAS  PubMed  Google Scholar 

  102. Sandell J, Zhu TC. A review of in-vio human optical properties and its impact on PDT. J Biophotonics. 2011;4:773–87.

    PubMed Central  PubMed  Google Scholar 

  103. Finlay JC, Foster TH. Effect of pigment packaging on diffuse reflectance spectroscopy of samples containing red blood cells. Opt Lett. 2004;29:965–7.

    CAS  PubMed  Google Scholar 

  104. Farrell T, Patterson M, Wilson B. A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo. Med Phys. 1992;19:879–88.

    CAS  PubMed  Google Scholar 

  105. Jacques S, Wang LH, Hielscher A. Time-resolved photon propagation in tissues. In: Optical_thermal response of laser-irradiated tissue. New York: Plenum Press; 1995.

    Google Scholar 

  106. Finlay JC, Foster TH. Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady-state diffuse reflectance at a single, short source-detector separation. Med Phys. 2004;31:1949–59.

    PubMed  Google Scholar 

  107. Dimofte A, Finlay JC, Zhu TC. A method determination of the absorption and scattering properties interstitially in turbid media. Phys Med Biol. 2005;50:2291–311.

    PubMed  Google Scholar 

  108. Boas DA, Brooks DH, Miller EL, DiMarzio CA, Kilmer M, Gaudette RJ, Zhang Q. Imaging the body with diffuse optical tomography. Signal Process Mag, IEEE. 2001;18:57–75.

    Google Scholar 

  109. Durduran T, Choe R, Culver JP, Zubkov L, Holboke M, Gaimmarco J, Chance B, Yodh A. Bulk optical properties of healthy female breast tissue. Phys Med Biol. 2002;47:2847–61.

    CAS  PubMed  Google Scholar 

  110. Wang KK, Zhu TC. Reconstruction of in-vivo optical properties for human prostate using interstitial diffuse optical tomography. Opt Express. 2009;17:11665–72.

    PubMed Central  CAS  PubMed  Google Scholar 

  111. Liang X, Wang KK-H, Zhu TC. Feasibility of interstitial diffuse optical tomography using cylindrical diffusing fibers for prostate PDT. Phys Med Biol. 2013;58:3461–80.

    PubMed Central  PubMed  Google Scholar 

  112. Cuccia DJ, Bevilacqua F, Durkin AJ, Tromberg BJ. Modulated imaging: quantitative analysis and tomography of turbid media in the spatial-frequency domain. Opt Lett. 2005;30:1354–6.

    PubMed  Google Scholar 

  113. Gioux S, Mazhar A, Lee BT, Lin SJ, Tobias AM, Cuccia DJ, Stockdale A, Oketokoun R, Ashitate Y, Kelly E, Weinmann M, Durr NJ, Moffitt La, Durkin AJ, Tromberg BJ, Frangioni JV. First-in-human pilot study of a spatial frequency domain oxygenation imaging system. J Biomed Opt. 2011;16:086015.

    PubMed Central  PubMed  Google Scholar 

  114. Zhou C, Yu G, Furuya D, Greenberg J, Yodh A, Durduran T. Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain. Opt Express. 2006;14:1125–44.

    PubMed  Google Scholar 

  115. Perelman LT, Backman V, Wallace M, Zonios G, Manoharan R, Nusrat A, Shields S, Seiler M, Lima C, Hamano T, Itzkan I, Van Dam J, Crawford JM, Feld MS. Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution. Phys Rev Lett. 1998;80:627–30.

    CAS  Google Scholar 

  116. Wilson JD, Bigelow CE, Calkins DJ, Foster TH. Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling. Biophys J. 2005;88:2929–38.

    PubMed Central  CAS  PubMed  Google Scholar 

  117. Wilson JD, Giesselman BR, Mitra S, Foster TH. Lysosome-damage-induced scattering changes coincide with release of cytochrome c. Opt Lett. 2007;32:2517–9.

    CAS  PubMed  Google Scholar 

  118. Woodhams JH, Kunz L, Bown SG, MacRobert AJ. Correlation of real-time haemoglobin oxygen saturation monitoring during photodynamic therapy with microvascular effects and tissue necrosis in normal rat liver. Br J Cancer. 2004;91:788–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Pham TH, Hornung R, Berns MW, Tadir Y, Tromberg BJ. Monitoring tumor response during photodynamic therapy using near-infrared photon-migration spectroscopy. Photochem Photobiol. 2001;73:669–77.

    CAS  PubMed  Google Scholar 

  120. Standish BA, Lee KK, Jin X, Mariampillai A, Munce NR, Wood MF, Wilson BC, Vitkin IA, Yang VX. Interstitial Doppler optical coherence tomography as a local tumor necrosis predictor in photodynamic therapy of prostatic carcinoma: an in vivo study. Cancer Res. 2008;68:9987–95.

    CAS  PubMed  Google Scholar 

  121. Yu G, Durduran T, Zhou C, Wang HW, Putt ME, Saunders HM, Sehgal CM, Glatstein E, Yodh AG, Busch TM. Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy. Clin Cancer Res. 2005;11:3543–52.

    CAS  PubMed  Google Scholar 

  122. Wang HW, Putt ME, Emanuele MJ, Shin DB, Glatstein E, Yodh AG, Busch TM. Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome. Cancer Res. 2004;64:7553–61.

    CAS  PubMed  Google Scholar 

  123. Mesquita RC, Han SW, Miller J, Schenkel SS, Pole A, Esipova TV, Vinogradov SA, Putt ME, Yodh AG, Busch TM. Tumor blood flow differs between mouse strains: consequences for vasoresponse to photodynamic therapy. PLoS One. 2012;7:e37322.

    PubMed Central  CAS  PubMed  Google Scholar 

  124. Konecky SD, Owen CM, Rice T, Valdés Pa, Kolste K, Wilson BC, Leblond F, Roberts DW, Paulsen KD, Tromberg BJ. Spatial frequency domain tomography of protoporphyrin IX fluorescence in preclinical glioma models. J Biomed Opt. 2012;17:056008.

    PubMed Central  PubMed  Google Scholar 

  125. Finlay JC, Zhu TC, Dimofte A, Stripp D, Malkowicz SB, Busch TM, Hahn SM. Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy. Photochem Photobiol. 2006;82:1270–80.

    CAS  PubMed  Google Scholar 

  126. Weersink RA, Hayward JE, Diamond KR, Patterson MS. Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy. Photochem Photobiol. 1997;66:326–35.

    CAS  PubMed  Google Scholar 

  127. Davis SC, Pogue BW, Dehghani H, Paulsen KD. Tissue drug concentration determines whether fluorescence or absorption measurements are more sensitive in diffuse optical tomography of exogenous contrast agents. Appl Opt. 2009;48:D262–72.

    PubMed Central  CAS  PubMed  Google Scholar 

  128. Wilson B, Patterson M, Lilge L. Implicit and explicit dosimetry in photodynamic therapy: a new paradigm. Lasers Med Sci. 1997;12:182–99.

    CAS  PubMed  Google Scholar 

  129. Georgakoudi I, Foster TH. Singlet oxygen- versus nonsinglet oxygen-mediated mechanisms of sensitizer photobleaching and their effects on photodynamic dosimetry. Photochem Photobiol. 1998;67:612–25.

    CAS  PubMed  Google Scholar 

  130. Robinson DJ, de Bruijn HS, van der Veen N, Stringer MR, Brown SB, Star WM. Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect. Photochem Photobiol. 1998;67:140–9.

    CAS  PubMed  Google Scholar 

  131. Boere IA, Robinson DJ, de Bruijn HS, Kluin J, Tilanus HW, Sterenborg HJ, de Bruin RW. Protoporphyrin IX fluorescence photobleaching and the response of rat Barrett’s esophagus following 5-aminolevulinic acid photodynamic therapy. Photochem Photobiol. 2006;82:1638–44.

    CAS  PubMed  Google Scholar 

  132. Cottrell WJ, Paquette AD, Keymel KR, Foster TH, Oseroff AR. Irradiance-dependent photobleaching and pain in delta-aminolevulinic acid-photodynamic therapy of superficial basal cell carcinomas. Clin Cancer Res. 2008;14:4475–83.

    PubMed Central  CAS  PubMed  Google Scholar 

  133. Baran TM, Foster TH. Fluence rate-dependent photobleaching of intratumorally administered Pc 4 does not predict tumor growth delay. Photochem Photobiol. 2012;88:1273–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Finlay JC, Mitra S, Foster TH. In vivo mTHPC photobleaching in normal rat skin exhibits unique irradiance-dependent features. Photochem Photobiol. 2002;75:282–8.

    CAS  PubMed  Google Scholar 

  135. Jarvi MT, Patterson MJ, Wilson BC. Insights into photodynamic therapy dosimetry: simultaneous singlet oxygen luminescence and photosensitizer photobleaching measurements. Biophys J. 2012;102:661–71.

    PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgements

Support during the preparation of this text was provided by NIH grants CA-085831 and CA 129554.

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Authors and Affiliations

  1. Radiation Biology Division, Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, Room 8-126 3400 Civic Center Blvd, Bldg 421, 19104, Philadelphia, PA, USA

    Shannon M. Gallagher‐Colombo & Assoc. Prof. Dr. Theresa M. Busch

  2. Radiation Physics Division, Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, 19104, Philadelphia, PA, USA

    Jarod C. Finlay

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  1. Shannon M. Gallagher‐Colombo
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  2. Jarod C. Finlay
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  3. Assoc. Prof. Dr. Theresa M. Busch
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Correspondence to Theresa M. Busch .

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Editors and Affiliations

  1. Medical and Biological Sciences, University of Udine, Udine, Italy

    Valentina Rapozzi

  2. Prof. Ghiretti, Universita Padova Ist. Biologia Animale, Padova, Italy

    Giulio Jori

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Gallagher‐Colombo, S., Finlay, J., Busch, T. (2015). Tumor Microenvironment as a Determinant of Photodynamic Therapy Resistance. In: Rapozzi, V., Jori, G. (eds) Resistance to Photodynamic Therapy in Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 5. Springer, Cham. https://doi.org/10.1007/978-3-319-12730-9_3

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