With photodynamic therapy (PDT), “no matter what you do, if you are lucky, there is a prodeath response,” stated Tayyaba Hasan, PhD, of the Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston. However, “simultaneously, there is a prosurvival molecular response, which mitigates the desired outcome with PDT,” she continued. Simply put, these opposing molecular responses are at the heart of the challenge for basic science researchers and clinicians to enhance the photodynamic effect.
In this article, Dr. Hasan explores the preclinical research findings on molecular targets that serve as the clinical foundation for moving PDT forward into the future, essentially in combination treatment. First, the molecular response to PDT in prostate, pancreatic, and ovarian cancer cell models is discussed, featuring the roles of both vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in guiding the selection of targeted agents to join PDT in combination. Second, the role of preconditioning via nuclear receptor targets, such as vitamin D and retinoic acid, before PDT to improve the photodynamic effect is briefly addressed.
del Carmen MG, Rizvi I, Chang Y et al.. Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo. J Natl Cancer Inst 2005;97:1516–1524.
Chang SK, Rizvi I, Solban N et al.. In vivo optical molecular imaging of vascular endothelial growth factor for monitoring cancer treatment. Clin Cancer Res 2008;14:4146–4153.
Abu-Yousif AO, Moor AC, Zheng X et al.. Epidermal growth factor receptor-targeted photosensitizer selectively inhibits EGFR signaling and induces targeted phototoxicity in ovarian cancer cells. Cancer Lett 2012;321:120–127.
Duska LR, Hamblin MR, Miller JL, Hasan T. Combination photoimmunotherapy and cisplatin: effects on human ovarian cancer ex vivo. J Natl Cancer Inst 1999;91:1557–1563.
Rizvi I, Celli JP, Evans CL et al.. Synergistic enhancement of carboplatin efficacy with photodynamic therapy in a three-dimensional model for micrometastatic ovarian cancer. Cancer Res 2010;70:9319–9328.
Zhong W, Celli JP, Rizvi I et al.. In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring. Br J Cancer 2009;101:2015–2022.
Celli JP, Solban N, Liang A et al.. Verteporfin-based photodynamic therapy overcomes gemcitabine insensitivity in a panel of pancreatic cancer cell lines. Lasers Surg Med 2011;43:565–574.
Evans CL, Abu-Yousif AO, Park YJ et al.. Killing hypoxic cell populations in a 3D tumor model with EtNBS-PDT. PLoS One 2011;6:e23434.
Ortel B, Chen N, Brissette J et al.. Differentiation-specific increase in ALA-induced protoporphyrin IX accumulation in primary mouse keratinocytes. Br J Cancer 1998;77:1744–1751.
Ortel B, Sharlin D, O’Donnell D et al.. Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells. Br J Cancer 2002;87:1321–1327.
Anand S, Honari G, Hasan T et al.. Low-dose methotrexate enhances aminolevulinate-based photodynamic therapy in skin carcinoma cells in vitro and in vivo. Clin Cancer Res 2009;15:3333–3343.
Anand S, Wilson C, Hasan T, Maytin EV. Vitamin D3 enhances the apoptotic response of epithelial tumors to aminolevulinate-based photodynamic therapy. Cancer Res 2011;71:6040–6050.