The Tumor Biology and Microenvironment (TBM) Program aims to eradicate cancer by identifying the cellular and molecular mechanisms that drive interactions between tumors and their microenvironments, and develop and test innovative diagnostic and treatment strategies. This highly integrated program includes 36 members from 16 WSU departments and $14,193,608 in grants, of which $5,908,215 is peer reviewed. The Program goals are addressed with three themes that encompass basic, preclinical, and clinical research. The first theme identifies and exploits the mechanisms that confer phenotypical plasticity and survival of tumor cells in tumor progression. Translational research is conducted to evaluate the potential clinical application of these molecular determinants as tumor markers and/or therapeutic targets. The second theme identifies and exploits the mechanisms that confer the unhealable wounding of tumor stroma. Our investigators identify and characterize factors in an extracellular proteolysis and signaling network that enable tumor cells to adapt to and subvert the microenvironment in the development of bone metastases. Key molecules in this network are evaluated to determine if they can be used to predict cancer progression and treatment outcomes. The third theme identifies and exploits the host immune response to tumor progression. Bispecific antibody-armed activated T-cells are tested in solid tumors and hematologic malignancies in the context of chemotherapy or high dose chemotherapy and stem cell transplantation. Anti-tumor DNA vaccines are developed and tested using mouse and domesticated cat models. Our investigators study immune modulators and inhibitors of adverse pro-inflammatory responses. Our members also develop novel vehicles to deliver immunotherapeutic agents. TBM Program members actively collaborate with members of the MI, MT, and PSDR Programs at KCI. Of the 612 manuscripts published from December 2010 to November 2014, 44% and 38% were intra- and inter-programmatic, respectively, and 27% were multi-institutional collaborations.

Public Health Relevance

In 2014, there were an estimated 1,665,540 new cancer cases diagnosed and 585,720 cancer deaths in the United States. Cancer remains the second most common cause of death in the US, accounting for nearly 1 of every 4 deaths (source: American Cancer Society). The Karmanos Cancer Institute is a unique, urban-based integrated center of research, patient care and education, dedicated to the prevention, early detection, treatment and eventual eradication of cancer. Key to achieving this mission is KCI's research effort which is conducted among four interdisciplinary Programs, organized to integrate basic, translational, and clinical research with population research-based cancer control activities.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA022453-37
Application #
9605726
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
Ptak, Krzysztof
Project Start
1997-08-08
Project End
2020-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
37
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Wayne State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Herroon, Mackenzie K; Rajagurubandara, Erandi; Diedrich, Jonathan D et al. (2018) Adipocyte-activated oxidative and ER stress pathways promote tumor survival in bone via upregulation of Heme Oxygenase 1 and Survivin. Sci Rep 8:40
Colacino, Justin A; Azizi, Ebrahim; Brooks, Michael D et al. (2018) Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling. Stem Cell Reports 10:1596-1609
Blocker, Stephanie J; Shields, Anthony F (2018) Imaging of Nanoparticle Distribution to Assess Treatments That Alter Delivery. Mol Imaging Biol 20:340-351
Guastella, Anthony R; Michelhaugh, Sharon K; Klinger, Neil V et al. (2018) Investigation of the aryl hydrocarbon receptor and the intrinsic tumoral component of the kynurenine pathway of tryptophan metabolism in primary brain tumors. J Neurooncol 139:239-249
Li, Feng; Wang, Yongli; Li, Dapeng et al. (2018) Perspectives on the recent developments with green tea polyphenols in drug discovery. Expert Opin Drug Discov 13:643-660
Ramseyer, Vanesa D; Kimler, Victoria A; Granneman, James G (2018) Vacuolar protein sorting 13C is a novel lipid droplet protein that inhibits lipolysis in brown adipocytes. Mol Metab 7:57-70
Healy, Mark A; Morris, Arden M; Abrahamse, Paul et al. (2018) The accuracy of chemotherapy ascertainment among colorectal cancer patients in the surveillance, epidemiology, and end results registry program. BMC Cancer 18:481
Lacher, Sarah E; Alazizi, Adnan; Wang, Xuting et al. (2018) A hypermorphic antioxidant response element is associated with increased MS4A6A expression and Alzheimer's disease. Redox Biol 14:686-693
Alsaab, Hashem O; Sau, Samaresh; Alzhrani, Rami M et al. (2018) Tumor hypoxia directed multimodal nanotherapy for overcoming drug resistance in renal cell carcinoma and reprogramming macrophages. Biomaterials 183:280-294
Chammaa, May; Malysa, Agnes; Redondo, Carlos et al. (2018) RUMI is a novel negative prognostic marker and therapeutic target in non-small-cell lung cancer. J Cell Physiol 233:9548-9562

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