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Photodynamic therapy (PDT) is a treatment (Castano et al., 2006; Gomer, 1989; Oleinick and Evans, 1998) that involves three components: a photoactivatable photosensitizer (PS), laser light, and tissue oxygen. The current applications of non-targeted PDT (ntPDT) involve intravenous injection or topical application of PS followed by irradiation of the diseased lesion with a laser light. Upon activation by laser light, PS converts intracellular oxygen to singlet oxygen ions, which then cause cellular necrosis and/or apoptosis. PDT has clinical indications in the treatment of localized cancers, such as breast cancer, and has therapeutic potential for local recurrence of chemoresistant tumors (Capella and Capella, 2003; Merlin et al., 2003). However, a serious limitation of conventional ntPDT is the toxicity that results from internalization of the PS by normal cells (Taber et al., 1998). To overcome the poor selectivity of PS, antibodies, ligands and peptides have been tested in order to develop targeted PDT (tPDT), which would target PS into tumor cells (Mayo et al., 2003; Sharman et al., 2004) or vascular endothelial cells alone (Bechet et al., 2010). To the best of our knowledge, there are no other published papers reporting the successful development of tPDT that can simultaneously target both the tumor neovasculature and tumor cells except for three recent articles (Duanmu et al., 2011; Hu et al., 2010, 2011) from our laboratory (Figure 1). Here we summarize the development, efficacy and safety tests of dual tumor neovasculatureand tumor cell-targeting PDT by targeting the receptor tissue factor (TF) using its natural ligand factor VII (fVII)conjugated photoactivable sensitizers for treatment of breast cancer in preclinical studies. We also review the selective expression of TF on angiogenic tumor vasculature and the percentages of TF on cancer cells in several most common solid tumors and leukemia, which we believe could help us to predict what percentage of patients with individual cancer can benefit from these TF-targeting therapies in future clinical trials and applications.

Factor VII-Targeted Photodynamic Therapy for Breast Cancer and Its Therapeutic Potential for Other Solid Cancers and Leukemia