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 - Career Development (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
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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Saadat, Nadia; Liu, Fangchao; Haynes, Brittany et al. (2018) Nano-delivery of RAD6/Translesion Synthesis Inhibitor SMI#9 for Triple-negative Breast Cancer Therapy. Mol Cancer Ther 17:2586-2597
Dedigama-Arachchige, Pavithra M; Acharige, Nuwan P N; Pflum, Mary Kay H (2018) Identification of PP1-Gadd34 substrates involved in the unfolded protein response using K-BIPS, a method for phosphatase substrate identification. Mol Omics 14:121-133
Burl, Rayanne B; Ramseyer, Vanesa D; Rondini, Elizabeth A et al. (2018) Deconstructing Adipogenesis Induced by ?3-Adrenergic Receptor Activation with Single-Cell Expression Profiling. Cell Metab 28:300-309.e4

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