The unifying feature of this Program Project remains its long-standing bench to bedside approach: to gain an increased understanding of photodynamic therapy (PDT) mechanisms and to translate it into optimized treatment. The unifying hypothesis is that the full potential of PDT of cancer cannot be realized without a comprehensive understanding of the interaction of the diverse mechanisms of molecular and cellular PDT responses. This Program Project has exceptionally broad, multidisciplinary expertise and is uniquely qualified to attempt to develop such a comprehensive view. The specific goals are: (i) The discovery and preclinical development of photoactivatable agents that lack prolonged general phototoxicity and provide a greater degree of efficacy and selectivity for treatment as well as diagnosis;(ii) The discovery of molecular and cellular mechanisms that can be translated into the design of improved photosensitizers and the rational design of combination therapies;(iii) The further development, translation and clinical application of our discovery that PDT and PDT generated anti-tumor vaccines can stimulate the adaptive anti-cancer immune response to support the local PDT effect with a systemic attack on the malignant tissue;(iv) The development of novel approaches to the treatment of non-melanoma skin cancer and H&N cancer. Five individual research projects will address the following questions: 1) Can we design and develop novel photosensitizing and imaging agents based on pyropheophorbides (HPPH;665 nm), purpurinimides (700 nm) and bacterio-purpurinimides (800 nm) that exhibit high efficacy and selectivity? 2) Can we identify regulatory pathways that are relevant in determining post-PDT survival of tumor cells and assess the impact of therapeutic interference with these pathways in controlling recurrence of tumor cell growth? 3) Can we understand the mechanisms by which PDT enhanced inflammation augments anti-tumor immunity and translate our findings to the clinic to enhance anti-tumor immunity and combat secondary disease? 4) Can we optimize the ALA-PDT treatment of non-melanoma skin cancer by choosing appropriate treatment strategies that consider perfusion and intra-tumor vascular and photosensitizer distributions, understanding mechanisms and constructing computational models for PDT? Can we enhance tumor control through addition of immune modulators and vaccination of patients with PDT treated cells? 5) Is PDT with the second generation photosensitize HPPH equal or superior to porfimer sodium PDT in controlling early cancer of the oral cavity and larynx, while sparing patients protracted sun avoidance? Can biomarkers be identified that correlate with treatment outcome? The projects are supported by three scientific cores and an Administrative Core.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA055791-20
Application #
8462208
Study Section
Special Emphasis Panel (ZCA1-GRB-P (O1))
Program Officer
Wong, Rosemary S
Project Start
1998-04-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
20
Fiscal Year
2013
Total Cost
$1,954,061
Indirect Cost
$785,782
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Shafirstein, Gal; Bellnier, David A; Oakley, Emily et al. (2018) Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer. Br J Cancer 119:1191-1199
Tracy, Erin C; Bowman, Mary-Jo; Pandey, Ravendra K et al. (2018) Cell-specific Retention and Action of Pheophorbide-based Photosensitizers in Human Lung Cancer Cells. Photochem Photobiol :
Shafirstein, Gal; Bellnier, David; Oakley, Emily et al. (2017) Interstitial Photodynamic Therapy-A Focused Review. Cancers (Basel) 9:
Saenz, Courtney; Cheruku, Ravindra R; Ohulchanskyy, Tymish Y et al. (2017) Structural and Epimeric Isomers of HPPH [3-Devinyl 3-{1-(1-hexyloxy) ethyl}pyropheophorbide-a]: Effects on Uptake and Photodynamic Therapy of Cancer. ACS Chem Biol 12:933-946
Oakley, Emily; Bellnier, David A; Hutson, Alan et al. (2017) Surface markers for guiding cylindrical diffuser fiber insertion in interstitial photodynamic therapy of head and neck cancer. Lasers Surg Med 49:599-608
Egan, Shawn M; Karasik, Ellen; Ellis, Leigh et al. (2017) miR-30e* is overexpressed in prostate cancer and promotes NF-?B-mediated proliferation and tumor growth. Oncotarget 8:67626-67638
Harris, Kassem; Oakley, Emily; Bellnier, David et al. (2017) Endobronchial ultrasound-guidance for interstitial photodynamic therapy of locally advanced lung cancer-a new interventional concept. J Thorac Dis 9:2613-2618
Hall, Brandon M; Balan, Vitaly; Gleiberman, Anatoli S et al. (2017) p16(Ink4a) and senescence-associated ?-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging (Albany NY) 9:1867-1884
Mimikos, Christina; Shafirstein, Gal; Arshad, Hassan (2016) Current state and future of photodynamic therapy for the treatment of head and neck squamous cell carcinoma. World J Otorhinolaryngol Head Neck Surg 2:126-129
Patel, Nayan; Pera, Paula; Joshi, Penny et al. (2016) Highly Effective Dual-Function Near-Infrared (NIR) Photosensitizer for Fluorescence Imaging and Photodynamic Therapy (PDT) of Cancer. J Med Chem 59:9774-9787

Showing the most recent 10 out of 167 publications