Achieving effective anticancer drug therapy requires achieving success in controlling at least three major physical properties: Toxicity within exposed cancer cells, delivery of the agent so as to exceed a threshold effective level of drug activity in the full anatomic extent of the cancer cell population, and limiting the side-effects affecting normal tissues. Recent preliminary data of our co-leaders indicates areas in which these critical barriers can be overcome. We found evidence for a severe limitation for effective drug penetration in pancreatic and perhaps other cancers. We developed new tools for a micro-anatomic understanding of drug delivery, methods to measure short-timed endpoints of drug effects, and ways to improve tumor-specific retention of delivered circulating agents. These developments create new opportunities addressed in our proposal. Our short-term Aims are to develop tools and understanding of the micro-anatomy and timing of drug penetration in GI cancers using patient and animal tumors, to manage better the toxicity of certain administered agents, and to improve drug delivery by and across the tumor vasculature. These studies are done in conjunction with four ongoing clinical trials (funded elsewhere) and may allow stratification of results from trials and the design of improved trials. Our long-term goal is to enable more efficacious treatment of GI cancers and to lay a foundation for using tissue-based drug-delivery assay as part of the routine lab accompaniments - the companion diagnostics - of cancer therapy.

Public Health Relevance

It is often said that cancers are frequently resistant to anti-cancer drugs. In most tumors, it is possible that this view is misleading. Improved delivery of anti-cancer drugs, and new test procedures so as to inform doctors about the progress towards effective delivery in individual patients, may provide fresh approach and improved treatment strategies for using a wide range of anti-cancer drugs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA062924-20
Application #
8559518
Study Section
Special Emphasis Panel (ZCA1-RPRB-M)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
20
Fiscal Year
2013
Total Cost
$340,582
Indirect Cost
$129,849
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Hata, Tatsuo; Dal Molin, Marco; Suenaga, Masaya et al. (2016) Cyst Fluid Telomerase Activity Predicts the Histologic Grade of Cystic Neoplasms of the Pancreas. Clin Cancer Res 22:5141-5151
Childs, Erica J; Chaffee, Kari G; Gallinger, Steven et al. (2016) Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study. Cancer Epidemiol Biomarkers Prev 25:1185-91
Yachida, Shinichi; Wood, Laura D; Suzuki, Masami et al. (2016) Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. Cancer Cell 29:229-40
Rucki, Agnieszka A; Foley, Kelly; Zhang, Pingbo et al. (2016) Heterogeneous stromal signaling within the tumor microenvironment controls the metastasis of pancreatic cancer. Cancer Res :
Faisal, Farzana; Tsai, Hua-Ling; Blackford, Amanda et al. (2016) Longer Course of Induction Chemotherapy Followed by Chemoradiation Favors Better Survival Outcomes for Patients With Locally Advanced Pancreatic Cancer. Am J Clin Oncol 39:18-26
Kumar, Abhijeet; Le, Dung T (2016) Hepatocellular Carcinoma Regression After Cessation of Immunosuppressive Therapy. J Clin Oncol 34:e90-2
Poruk, Katherine E; Blackford, Amanda L; Weiss, Matthew J et al. (2016) Circulating Tumor Cells Expressing Markers of Tumor Initiating Cells Predict Poor Survival and Cancer Recurrence in Patients with Pancreatic Ductal Adenocarcinoma. Clin Cancer Res :
Masica, David L; Dal Molin, Marco; Wolfgang, Christopher L et al. (2016) A novel approach for selecting combination clinical markers of pathology applied to a large retrospective cohort of surgically resected pancreatic cysts. J Am Med Inform Assoc :
Poruk, Katherine E; Valero 3rd, Vicente; Saunders, Tyler et al. (2016) Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma. Ann Surg 264:1073-1081
Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth et al. (2016) Current progress in immunotherapy for pancreatic cancer. Cancer Lett 381:244-51

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