Pancreatic cancer accounts for 5% of cancer deaths in the United States and is the fourth leading cause of cancer mortality. According to the SEER Cancer Statistics Review, it is estimated that in 2009 there will have been over 42,000 new cases of pancreatic cancer and over 35,000 deaths. Current treatment options are of limited benefit with a 5-year survival rate following diagnosis of less than 5%. The current standard-of-care therapy, gemcitabine, only improves survival by a few weeks. It is clear that more effective therapy for the treatment of pancreatic cancer is needed. Ultrasound-enhanced drug delivery is an active and promising area of research. Ultrasound has been demonstrated to enhance vascular permeability and drug penetration into tissue, primarily due to mechanisms related to cavitation. Ongoing research efforts (including preliminary data from our lab presented in this proposal) have identified ultrasound mechanism and parameters that are likely to be effective in vivo. Several in vivo studies have been performed in various xenograft and syngenic autograft animal models that have demonstrated that ultrasound enhanced drug delivery is effective in decreasing tumor size and increasing survival duration;however, these tumor models, especially for pancreatic cancer, have been criticized for being unrealistic and not representative of the true in vivo environment seen in the human disease. In this proposal, we believe that we have developed a study that includes rigorous fundamental science, but also is rapidly translatable. The attractiveness of the strategy in this proposal is that it utilizes a chemotherapeutic agent that is the current standard of care (gemcitabine) along with focused ultrasound technology that is currently available and readily implementable to rapidly translate these results into human clinical trials. In addition, it brings for the first time to the study of ultrasound-enhanced drug delivery a unique and realistic animal model (KPC mice), which will provide much more realistic data to evaluate the potential for clinical translation. The overall aim of this proposal is to investigate whether ultrasound can enhance targeted drug penetration into an in vivo pancreatic tumor and improve survival duration. We believe that the successful accomplishment of the specific aims of this proposal will be a major step toward applying this promising approach to human patients who are suffering from pancreatic cancer.

Public Health Relevance

Pancreatic cancer accounts for 5% of cancer deaths in the United States and is the fourth leading cause of cancer mortality and current treatments are essentially ineffective. The overall aim of this proposal is to investigate whether ultrasound can enhance targeted drug penetration into an in vivo pancreatic tumor and improve survival duration. We believe that the successful accomplishment of the specific aims of this proposal will be a major step toward applying this promising approach to human patients who are suffering from pancreatic cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA154451-03
Application #
8531683
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Tandon, Pushpa
Project Start
2011-09-14
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$509,766
Indirect Cost
$155,425
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Li, Tong; Chen, Hong; Khokhlova, Tatiana et al. (2014) Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors. Ultrasound Med Biol 40:1523-34
Li, Tong; Khokhlova, Tatiana D; Sapozhnikov, Oleg A et al. (2014) A new active cavitation mapping technique for pulsed HIFU applications--bubble Doppler. IEEE Trans Ultrason Ferroelectr Freq Control 61:1698-708