Table 1.

Angiogenic inhibitors investigated in combination with PDT and their therapeutic outcome

	Tumor model	Photosensitizer	Growth factors investigated	Angiogenesis inhibitor	Findings	Reference
1	BA mouse mammary carcinoma	Photofrin	VEGF, HIF-1α	EMAP-II and IM862	Improved tumoricidal response was observed	Ferrario et al. [12]
2	Intracranial glioblastoma	Photofrin	VEGFR-1 and VEGFR-2	MF1 and DC101	Noted significant inhibition of tumor growth and extended survival of mice	Jiang et al. [31]
3	Prostate tumor	Liposomal BPD	VEGF	TNP-470	Combination treatment abolished the increase in VEGF levels caused by subcurative PDT and reduced local tumor growth	Kosharskyy et al. [36]
4	Nasopharyngeal and bladder carcinoma	Hypericin	VEGF, bFGF, HIF-1α	SU5416 and SU6668	Extended survival of tumor-bearing host mice was noted	Zhou et al. [40]
5	Kaposi’s sarcoma	Photofrin	VEGF	Avastin (bevacizumab)	Improved PDT treatment effectiveness	Ferrario and Gomer [28]
6	Prostate and pancreatic carcinoma	Benzoporphyrin derivative	VEGF	Avastin	Successfully monitored treatment-induced changes in VEGF expression using optical molecular imaging system	Chang et al. [37]
7	Bladder carcinoma (MGH)	Hypericin	VEGF	Avastin	Improved tumor responsiveness was observed due to downregulation of VEGF, bFGF and EGF	Bhuvaneswari et al. [38]
8	Murine mammary 16c tumor	Hexylether pyropheophorbide-PDT	Receptor tyrosine kinase	PD166285 and PD173074	Potentiated anti-angiogenic and anti-tumor activity and prolonged the duration of anti-tumor response	Dimitroff et al. [66]
9	RIF tumors	Photofrin	COX-2, VEGF	NS-398	Enhanced PDT responsiveness in RIF tumors without increasing toxicity to normal tissue	Ferrario et al. [46]
10	BA mouse mammary carcinoma	Photofrin	COX-2	Celecoxib and NS-398	Improved in vivo PDT responsiveness by decreasing expression of angiogenic and inflammatory molecules	Ferrario et al. [67]
11	Colon adenocarcinoma	Photofrin	COX-2	Rofecoxib, NS-398 and nimesulide	Administration of nimesulide after illumination potentiated antitumor effects of Photofrin PDT	Makowski et al. [68]
12	Nasopharyngeal carcinoma	Hypericin	COX-2, VEGF and HIF-1α	Celecoxib	Administration of Celecoxib, 6 h post-PDT downregulated proangiogenic growth factors	Yee et al. [30]
13	Oral squamous cell carcinoma	ALA	COX-2	Nimesulide	Combination of ALA-PDT and nimesulide showed inhibitory effect on HSC-2 cells	Akita et al. [69]
14	Urinary bladder and cervix carcinoma	Hypericin	COX-2	p38 MAPK inhibitor PD169316	Improved the therapeutic efficacy of PDT by blocking COX-2 up-regulation	Hendrickx et al. [48]
15	Colon carcinoma	Mono-l-aspartyl chlorine e6	COX-2, IL-2	NS-398	Significantly decreased the weight of colon-38 tumor xenografts	Harvey et al. [70]
16	BA mouse mammary carcinoma	Photofrin	MMPs	Prinomastat (AG-3340)	Significantly improved PDT-mediated tumor response	Ferrario et al. [51]
17	Breast cancer tumors	Photofrin	Akt phosphorylation	PI3-K inhibitors	In vitro and in vivo PDT treatments induced Akt phosphorylation. PI3-K inhibitors blocked Akt phosphorylation by increasing apoptosis	Bozkulak et al. [64]